Nucleoside analogue reverse transcriptase inhibitors (NRTIs) have substantially lowered the risk of the mother-to-child transmission of HIV. Evidence of mitochondrial toxicity in vitro, in animal models and in adult HIV-infected patients, has raised concern about the perinatal safety of these antiretrovirals. In zidovudine-exposed, but HIV-uninfected infants, transient anaemia and additional long-term blood abnormalities (neutropenia, thrombopenia and lymphopenia) and hyperlactatemia have been documented. The overall risk of mortality and congenital abnormalities does not appear to be increased, but rare mitochondrial events cannot be excluded for lack of statistical power. French data suggest an above background incidence of mitochondrial symptomatology. Preclinical data demonstrate zidovudine also to be a carcinogen. Long-term systematic follow-up of exposed babies in large cohorts is needed, as are randomised trials with NRTIs carrying a lower risk of mitochondrial toxicity.