Human T-lymphotropic virus type I (HTLV-I) and type II (HTLV-II) are closely related retroviruses with similar biological properties and common modes of transmission. HTLV-I infection is endemic in well-defined geographic regions, and it is estimated that some 20 million individuals are infected worldwide. Although most infected individuals are asymptomatic carriers, some 2 to 5% will develop a chronic encephalomyelopathy, HTLV-I–associated myelopathy/tropical spastic paraparesis (HAM/TSP). In contrast with HTLV-I, the role of HTLV-II in the development of neurological disorders is much less clear. HTLV-II is endemic in many native Amerindian groups and epidemic in injecting drug users (IDUs) worldwide. To evaluate the role of HTLV-II in neurological disease, we have critically reviewed all reported cases of HTLV-II–associated disorders. This has confirmed that although rare infection is associated with a disorder clinically similar or identical to HAM/TSP. However, most reports that have attributed infection to a range of other neurological disorders are difficult to evaluate in that in many cases either the association appears to be fortuitous or the presentations were confounded by a background of concomitant human immunodeficiency virus–1 infection and/or active IDU. In view of the many HTLV-II–infected individuals in urban areas of North America and Europe, neurologists should be aware of the potential clinical consequences of this infection.