The English word finger has two senses, even in the context of appendages of a single typical human hand: 1) Any of the five terminal members of the hand. 2) Any of the four terminal members of the hand, other than the thumb.

Linguistically, it appears that the original sense was the first of these two: *penkwe-ros (also rendered as *penqrós) was, in the inferred Proto-Indo-European language, a suffixed form of *penkwe (or *penqe), which has given rise to many Indo-European-family words (tens of them defined in English dictionaries) that involve, or stem from, concepts of fiveness.

The thumb shares the following with each of the other four fingers:
• Having a skeleton of phalanges, joined by hinge-like joints that provide flexion toward the palm of the hand
• Having a dorsal surface that features hair and a nail, and a hairless palmar aspect with fingerprint ridges
The thumb contrasts with each of the other four fingers by being the only one that:
• Is opposable to the other four fingers
• Has two phalanges rather than three. However, recently there have been reports that the thumb, like other fingers, has three phalanges, but lacks a metacarpal bone.
• Has greater breadth in the distal phalanx than in the proximal phalanx
• Is attached to such a mobile metacarpus (which produces most of the opposability)
• Curls horizontally instead of vertically
and hence the etymology of the word: *tum is Proto-Indo-European for 'swelling' (cf 'tumor' and 'thigh') since the thumb is the stoutest of the fingers.

Anatomists and other researchers focused on human anatomy have hundreds of definitions of opposition. Some anatomists restrict opposition to when the thumb is approximated to the fifth finger (little finger) and refer to other approximations between the thumb and other fingers as apposition. To anatomists, this makes sense as two intrinsic hand muscles are named for this specific movement (the opponens pollicis and opponens digiti minimi respectively).

Other researchers use another definition, referring to opposition-apposition as the transition between flexion-abduction and extension-adduction; the side of the distal thumb phalanx thus approximated to the palm or the hand's radial side (side of index finger) during apposition and the pulp or "palmar" side of the distal thumb phalanx approximated to either the palm or other fingers during opposition.

Moving a limb back to its neutral position is called reposition and a rotary movement is referred to as circumduction.

Primatologists and hand research pioneers John and Prudence Napier defined opposition as: "A movement by which the pulp surface of the thumb is placed squarely in contact with – or diametrically opposite to – the terminal pads of one or all of the remaining fingers." For this true, pulp-to-pulp opposition to be possible, the thumb must rotate about its long axis (at the carpometacarpal joint). Arguably, this definition was chosen to underline what is unique to the human thumb.
• Primates fall into one of six groups:
The spider monkey compensates for being virtually thumbless by using the hairless part of its long, prehensile tail for grabbing objects. In apes and Old World monkeys, the thumb can be rotated around its axis, but the extensive area of contact between the pulps of the thumb and index finger is a human characteristic.

Darwinius masillae, an Eocene primate transitional fossil between prosimian and simian, had hands and feet with highly flexible digits featuring opposable thumbs and halluces.
• Giant pandas — five clawed fingers plus an extra-long sesamoid bone beside the true first finger that, though not a true finger, works like an opposable thumb.
• Most rodents have a partly opposable toe on each front paw, letting them grasp.
Additionally, in many polydactyl cats, both the innermost toe and outermost toe (pinky) may become opposable, allowing the cat to perform more complex tasks.
• In most phalangerid marsupials (a family of possums) except species Trichosurus and Wyulda, the first and second toes of the forefoot are opposable to the other three. In the hind foot, the …

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A primitive autonomization of the first carpometacarpal joint (CMC) may have occurred in dinosaurs. A real differentiation appeared an estimated 70 mya in early primates, while the shape of the human thumb CMC finally appears about 5 mya. The result of this evolutionary process is a human CMC joint positioned at 80° of pronation, 40 of abduction, and 50° of flexion in relation to an axis passing through the second and third CMC joints.

Opposable thumbs are shared by some primates, including most catarrhines. The climbing and suspensory behaviour in orthograde apes, such as chimpanzees, has resulted in elongated hands while the thumb has remained short. As a result, these primates are unable to perform the pad-to-pad grip associated with opposability. However, in pronograde monkeys such as baboons, an adaptation to a terrestrial lifestyle has led to reduced finger length and thus hand proportions similar to those of humans. Consequently, these primates have dexterous hands and are able to grasp objects using a pad-to-pad grip. It can thus be difficult to identify hand adaptations to manipulation-related tasks based solely on thumb proportions.

The evolution of the fully opposable thumb is usually associated with Homo habilis, a forerunner of Homo sapiens. This, however, is the suggested result of evolution from Homo erectus (around 1 mya) via a series of intermediate anthropoid stages, and is therefore a much more complicated link.

Modern humans are unique in the musculature of their forearm and hand. Yet, they remain autapomorphic, meaning each muscle is found in one or more non-human primates. The extensor pollicis brevis and flexor pollicis longus allow modern humans to have great manipulative skills and strong flexion in the thumb.

However, a more likely scenario may be that the specialized precision gripping hand (equipped with opposable thumb) of Homo habilis preceded walking, with the specialized adaptation of the spine, pelvis, and lower extremities preceding a more advanced hand. And, it is logical that a conservative, highly functional adaptation be followed by a series of more complex ones that complement it. With Homo habilis, an advanced grasping-capable hand was accompanied by facultative bipedalism, possibly implying, assuming a co-opted evolutionary relationship exists, that the latter resulted from the former as obligate bipedalism was yet to follow. Walking may have been a by-product of busy hands and not vice versa.

HACNS1 (also known as Human Accelerated Region 2) is a gene enhancer "that may have contributed to the evolution of the uniquely opposable human thumb, and possibly also modifications in the ankle or foot that allow humans to walk on two legs". Evidence to date shows that of the 110,000 gene enhancer sequences identified in the human genome, HACNS1 has undergone the most change during the human evolution since the chimpanzee–human last common ancestor.