Obesity is a serious chronic disease that has numerous etiologies. The prevalence of obesity has increased dramatically since about 1980 in the United States and worldwide in both developed and developing countries. This rapid spread is compatible with an infectious origin. This review discusses the 5 animal viruses and 3 human viruses that have been shown to cause obesity and examines the evidence to date for virus-induced obesity. The obesogenic animal viruses include canine distemper virus, Rous-associated virus type 7, Borna disease virus, scrapie agent, and SMAM-1. The first 4 viruses attack the central nervous system to produce obesity. SMAM-1, an avian adenovirus from India, acts directly on adipocytes and is the only animal virus that is associated with human obesity. The 3 human adenoviruses, adenovirus (Ad) 36, Ad-37, and Ad-5, that are associated with obesity also affect adipocytes directly. These viruses stimulate enzymes and transcription factors that cause accumulation of triglycerides and differentiation of preadipocytes into mature adipocytes. Ad-5 and Ad-37 have been shown to cause obesity in animals. Ad-36 has been studied the most and is the only human adenovirus to date that has been linked with human obesity. Ad-36 causes obesity in chickens, mice, rats, and monkeys and was present in 30% of obese humans and 11% of nonobese humans. In twins discordant for infection with Ad-36, the infected twins were heavier and fatter than their cotwins. The growing body of evidence demonstrating that viruses produce human obesity supports the concept that at least some of the worldwide epidemic of obesity in the past 25 years is due to viral infections.