The history of antiviral and antiretroviral therapy is recent compared with many other medical therapies, including traditional antibiotics in pregnancy. There are few long-term data on which to base decisions of management in pregnancy. Accessing up-to-date information is critical to optimizing the safety of care for mothers and their infants. Exposure to medications in pregnancy can be toxic to a fetus in a gestational age-dependent manner. Determination of safe medications for pregnancy must take into consideration the need for certain medications and the possibility of inadvertent exposure in early pregnancy because of unplanned pregnancies. This article reviews the most commonly used antiviral and antiretroviral agents and places emphasis on the issues regarding use in pregnancy.