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The probability of HIV transmission depends on the interplay of many different factors related to infectiousness of the HIV-infected partner, susceptibility of the HIV-uninfected partner, and biological characteristics of HIV strains. Here, we review recent studies of host immunological and genetic factors which may affect susceptibility to HIV-1 infection. These factors are summarized in Table 1. We propose how to explore biological correlates of susceptibility to HIV-1 infection in epidemiological studies, discuss the strengths and limitations of this research, and address the implications for public health