Most individuals exposed to human immunodeficiency virus (HIV), adults and children alike, do not become infected. Understanding the basis of this protection depends on systematically and comprehensively defining factors that determine the infectiousness of the host and the susceptibility of the recipient. Successful transmission depends on the relative balance between infectiousness and susceptibility, both of which are influenced by biologic, behavioral, and environmental factors. In this review, we discuss the advantages and disadvantages of mother‐to‐child HIV transmission as a model in which to elucidate correlates of immune protection.