Breastfeeding is a critical child survival intervention. The potential for transmission of some viral infections from mother-to-child, however, presents the dilemma of how best to interpret the benefits and risks of breastfeeding in different settings. Here, we compare the transmission dynamics, risk factors and outcomes of infection with three chronic viruses transmitted through breast milk: cytomegalovirus (CMV), human T-cell lymphotropic virus type 1 (HTLV-1), and human immunodeficiency virus (HIV). We provide an overview of current intervention approaches and discuss scientific, policy and programming gaps in our understanding of these major global infections.