Debilitating disorders of the nervous system have a relatively high prevalence in the tropics, a geographic region that is often deficient in specialists in the fields of neurology and epidemiology. During World War II, attention was called to a possible nutritional origin for most of these diseases. Recently, however, human T lymphotropic virus type I (HTLV-I), formerly linked only to a rare form of leukemia (adult T cell leukemia), has been associated with a spastic paraplegia observed mostly in tropical areas and referred to as tropical spastic paraparesis. This entity is also observed in nontropical areas endemic for HTLV-I, including Japan, South America, and the southern United States. Viruses of the HTLV family are being associated increasingly with pathology in humans. The pathogenesis of HTLV-I-associated tropical spastic paraparesis remains to be understood. However, future research is expected to favor a multidisciplinary approach, with exciting potential insights derived from the fields of neurology, immunology, and infectious diseases. The aim of this review is to summarize contemporary research related to the viral etiology of this clinical entity.