US immigrants of Caribbean origin are overrepresented in the HIV/AIDS prevalence statistics. Bidirectional travel between the United States and the Caribbean region by providing opportunities for sexual mixing may contribute to these high HIV rates. Caribbean immigrants face further risk because of limited health care access, social isolation, and stigma. Additionally, although substance abuse may not represent a major health issue in their countries of origin, Caribbean immigrants are composed disproportionately of adolescents who are at greatest risk of substance abuse. There is little information on the health care characteristics of these migrants, especially regarding HIV care. This article describes how the social and economic circumstances that surround the lives of people from the Caribbean and the challenges of the acculturation process have placed these individuals at risk of substance abuse and HIV infection. The article draws on findings from the literature and analysis of data from several sources.