In American Western culture, the bison is commonly referred to as "buffalo"; however, this is a misnomer. Though both bison and buffalo belong to the same family, Bovidae, the term 'buffalo' properly applies only to the Asian Water Buffalo and African Buffalo. The gaur, a large, thick-coated ox found in Asia, is also known as the Indian Bison, although it is in the genus Bos and thus not a true bison.

For our purpose we will still be using the term "Buffalo" or "American Buffalo".

Bison have a shaggy, dark brown winter coat, and a lighter weight, lighter brown summer coat. Bison can reach up to 2 metres (6½ ft) tall, 3 metres (10 ft) long and weigh 900 to 2,000 lbs (400 to 900 kg). The biggest specimens on record have weighed as much as 1140 kg (2,500 lb). The heads and forequarters are massive, and both sexes have short, curved horns, which they use in fighting for status within the herd and for defense. Bison mate in August and September; a single reddish-brown calf is born the following spring, and it nurses for a year. Bison are mature at three years of age, and have a life expectancy of approximately 15 years in the wild and up to 25 years in captivity.

One very rare condition is the white buffalo, where the calf turns entirely white. It is not to be confused with albino, since white bison still possess pigment in the skin, hair, and eyes. White bison are considered sacred by many Native Americans.

Due to its size and the protection afforded by living in a herd, the bison have few enemies besides humans. Grizzly bears and wolves may attempt to attack young calves or subadults, but only in the dead of winter when the herd cannot expend the energy to protect stragglers. A wolf pack can also take down an adult bison. Wolves frequently test even the largest bison for weaknesses; usually several wolves may pursue a bison and attempt to bring it down after the bison has succumbed to exhaustion or wounds from the wolves' bites

Bison are now raised for meat and hides. Over 250,000 of the 350,000 remaining bison are being raised for human consumption. Bison meat is lower in fat and cholesterol than beef which has led to the development of beefalo, a fertile cross-breed of bison and domestic cattle. In 2005, about 35,000 bison were processed for meat in the U.S., with the National Bison Association and USDA providing a "Certified American Buffalo" program with birth-to-consumer tracking of bison via RFID ear tags. There is even a market for kosher bison meat; these bison are slaughtered at one of the few kosher mammal slaughterhouses in the U.S., such as at AgriProcessors in Postville, Iowa, and the meat is then distributed nationwide.

Recent genetic studies of privately owned herds of bison show that many of them include animals with genes from domestic cattle; there are as few as 12,000 to 15,000 pure bison in the world. The numbers are uncertain because the tests so far used mitochondrial DNA analysis, and thus would miss cattle genes inherited in the male line; most of the hybrids look exactly like purebred bison. Even the herd on Santa Catalina Island, isolated since 1924 after being brought there for a movie shoot, were found to be mostly crossbreeds.

Custer State Park in South Dakota is home to 1,500 bison, one of the largest publicly held herds in the world.

A proposal known as Buffalo Commons has been suggested by a handful of academics and policymakers to restore large parts of the drier portion of the Great Plains to native prairie grazed by bison. Proponents argue that current agricultural use of the shortgrass prairie is not sustainable, pointing to periodic disasters such as the Dust Bowl and continuing significant population loss over the last 60 years. However, this plan is opposed by most who live in the areas in question.

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