The provision of antiretroviral drugs for the prevention of mother-to-child HIV transmission has been rising sharply in low- and middle-income countries. Changes to the World Health Organization guidelines support further extension of these programs. The result will be a greatly expanded population of HIV-exposed but uninfected children with substantial exposure to antiretroviral drugs, both in utero and while breastfeeding. There are limited data on possible toxicities in this burgeoning population, and the large number of confounding factors limits any conclusions. Although the evidence on birth defects and mitochondrial toxicity remains equivocal, considerable data link protease inhibitors to preterm delivery and low birth-weight. Transient hematologic toxicities are also likely. The drug impact later in life is an open question. Larger and longer cohort studies are necessary to properly balance the risks and benefits of large-scale infant exposure to antiretroviral agents.