The relationship between gender and health is a deeply interdependent one. Yet research in this area has focused primarily on how gender relations determine health behaviour and health outcomes. This article advocates a more holistic approach that conceptualises gender and health as fully intertwined and mutually constitutive. This interplay is explored through the case of HIV serodiscordance in which one person in a relationship is HIV positive and the other HIV negative. Drawing on in-depth research with discordant couples in urban Uganda, this study indicates that living with discordance can both reinforce and challenge normative gender power dynamics in relationships. This study, therefore, illustrates how significant health problems can influence gender relations. As such, it reveals the dialectical relationship between gender and health and also provides important insights for HIV prevention in the new era of antiretroviral treatment as prevention.