In complete contrast to past morphological studies, which tended to place Bradypus as the sister group to all other folivorans, molecular studies place them nested within the sloth superfamily Megatherioidea, making them the only surviving members of that radiation.

Recent phylogenetic analyses support the morphological data from the 1970s and 1980s that the two genera are not closely related and that each adopted their arboreal lifestyles independently.

[7] Understanding of sloth phylogeny has recently been greatly revised by molecular studies, based on collagen[3] and mitochondrial DNA[2] sequences.

[3][2] These results provide further strong support for the long-held belief that arboreality arose separately in the two genera via convergent paths.

[8] Three-toed sloths are about the size of a small dog or a large cat, with the head and body having a combined length of around 45 cm (18 in) and a weight of 3.5–4.5 kg (8–10 lb).

Unlike the two-toed sloths, they also have short tails of 6–7 cm (2–3 in), and they have three clawed toes on each limb.

[11] This means that they struggle to support their body weight when walking on all four limbs, so traveling on the ground is a dangerous and laborious process.

Large, curved claws and muscles specifically adapted for strength and stamina help sloths to keep a strong grip on tree branches.

[13] The abdominal organs close to their diaphragm (such as their stomach, liver, and kidneys) are attached to their lower ribs (or pelvic girdle in the latter case) by fibrinous adhesions, which prevent the weight of these organs from compressing their lungs when hanging, making inhalation easier.

[16] Because of their slow metabolism, they do not need to ingest many leaves on a daily basis, but when ambient temperatures are high, the symbiotic microbes and bacteria present in their gut will break down and ferment food at a faster rate.

[20] The home ranges used by wild brown-throated three-toed sloths in Costa Rica include cacao, pasture, riparian forests, peri-urban areas, and living fence-rows.

[27] Three-toed sloths are unusual amongst mammals in possessing as many as nine cervical vertebrae, which may be due to mutations in the homeotic genes.

[30] Firmicutes and Proteobacteria are the main bacterial phyla that dominate the sloth gut microbiome, which is less diverse than in many other herbivores.

[31] In addition to the gut microbiome, three-toed sloths have a symbiotic relationship with the unique ecosystem that grows on their fur.