Cuban DHF/DSS outbreaks have provided evidence of a reduced risk of people of Negroid race for DHF/DSS compared to those of Caucasoid race. These observations from Cuban dengue outbreaks have significant epidemiological interest, as the differences in susceptibility to DHF/DSS among racial groups in Cuba coincide with that reported in African and Black Caribbean populations. In this article, we review the literature on race as a risk factor for DHF/DSS and discuss recent results from ongoing studies. Taking into consideration the origins of contemporary Cuban inhabitants, we propose that the Cuban, Caribbean Black and African populations share a common gene pool that could explain, at least partially, the low incidence of dengue hemorrhagic fever in Cuba and Caribbean and African countries. The central role played by immunological mechanisms in the pathogenesis of DHF/DSS has led us to consider that the polymorphic genes associated with the immune response must be carefully considered among those human genes regulating dengue disease severity that might be distributed unequally in Blacks and Whites.