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. Key messages: • Three viruses are known to be transmitted through breastfeeding and to result in chronic infection: CMV, HTLV-1 and HIV. • CMV transmission through breast milk mostly leads to subclinical infection, except in preterm infants in whom severe clinical disease can occur; the best preventive and treatment approaches in this group remain unclear and more data are needed on long-term sequelae. • HTLV-1 is restricted to specific geographic foci and can be transmitted from mother-to-child through breastfeeding in 10-25% of cases; the best preventive strategy is avoidance or shortening of breastfeeding where safe alternatives are available. • The absolute transmission risk of HIV through breastfeeding in the context of suppressive maternal antiretroviral therapy is now low, even over extended periods. • Guidance for infant feeding for women living with HIV varies by setting: in low-and middle-income countries, breastfeeding with suppressive ART and adherence support is recommended, while in high-income settings formula feeding is advised.