Women in Africa are at a relatively higher risk of being infected with human immunodeficiency virus (HIV) compared to men. The current chapter aims at discussing factors that may contribute to this elevated risk. We first outline the biological (e.g. physiological and hormonal), sociocultural practices and norms and economic factors that place females at a disadvantage. We then review some of the interventions that have been found to be or are currently being tested as being ‘gender sensitive’, and have the potential of significantly reducing risk levels among females. Interventions discussed herein include biomedical, socioeconomic, behavioural and social protection measures.