Four genera of true chameleons have been described: Bradypodion, Brookesia, Chamaeleo, and Rhampholeon. Two additional genera (Calumma and Furcifer) are recognized by some researchers. More than 150 species are currently known, and additional ones remain to be named. About half of the species occur only in Madagascar, whereas others occur mostly in sub-Saharan Africa. Two species occur in Asia; one is native to southern India and Sri Lanka (Chamaeleo zeylanicus), and the other (the European chameleon, C. chamaeleon) is found from the Middle East to southern Spain. The most familiar chameleons belong to the genus Chamaeleo, and these have prehensile tails that wrap in a coil-like fashion around limbs to maintain balance. In contrast, most species of pigmy chameleons in the genera Brookesia (Madagascar) and Rhampholeon (Africa) have short stubby tails that are not prehensile; however, pigmy chameleons in Bradypodion have longer tails that are prehensile.

Most chameleons are 17–25 cm (7–10 inches) long, and the longest grows to 60 cm (24 inches). The body is laterally compressed, the tail is sometimes curled, and the bulged eyes move independently of one another. Also, some chameleons possess helmet-shaped heads.

Each species is capable of undergoing a particular range of colour (coloration) change. The mechanism involves the dispersal or concentration of pigment granules (melanophore cells) in the cells (cell) that contain them. These cells are under the control of the autonomic nervous system. Colour change is determined by such environmental factors as light and temperature as well as by emotions—such as fright and those associated with victory or defeat in battle with another chameleon. Many chameleons can assume a green, yellow, cream, or dark brown coloration. Frequently, this occurs with lighter or darker spots on the background colour of the body. Some of the most striking colours appear in males during mating. Some achieve colour patterns that are so vivid and complex that it is hard to imagine that they serve any natural purpose. It is a popular misconception that the chameleon changes its colour to match that of the background.

The chameleon's specialized vision and a specialized tongue-projection system permit the capture of insects and even birds from a distance. The chameleon's eyes are very good at detecting and regulating light. The lens of a chameleon's eye is capable of focusing extremely rapidly, and it can enlarge visual images much like a telephoto lens. Although many other lizards also use the tongue to capture prey, most can expel it only a short distance. In contrast, chameleons can launch their tongues at great speed to a distance of more than twice their body length, and they can strike and capture their prey with great accuracy. The hydrostatic force resulting from rapid contraction of a ringed accelerator muscle is used to project the tongue toward the chameleon's prey; a sticky tongue tip adheres to the victim's body; and strong retractor muscles pull the tongue and prey back into the mouth.

Most species are egg layers. Typically, females descend from their shrub or tree to bury between 2 and 40 eggs in the soil or rotting logs, and incubation lasts about three months. Some species, such as the large Jackson's chameleon (C. jacksonii), bear their young live; however, they do this without a placenta between the mother and the developing young. All nutrients (nutrient) necessary for development are contained within the egg itself, which simply develops within the female's oviduct minus a shell.

In addition, the Madagascan chameleon, F. labordi, has been widely acknowledged as the vertebrate with the shortest life span. The eggs of F. labordi hatch in November, and the young chameleons grow extremely fast; they mature to adulthood just two months later. After an intense competition for mates, eggs are laid in February, and the entire adult population perishes.