There is empirical evidence for a role for serotonin in autism. In experimental animals, early life exposure to serotonergic antidepressants or maternal stress affects brain development, with subsequent changes in serotonin tone in adult animals. Recently, antidepressant exposure during pregnancy has been associated with autism in epidemiological studies. At least part of the association is potentially explained by maternal depression or factors associated with depression. Importantly, even if there is no causal relation between prenatal antidepressant exposure and autism, use of antidepressants during pregnancy is a marker of potential problems later in life across five independent study populations, and exposed children may need special attention regardless of the underlying mechanism. Future studies need to disentangle the effects of maternal depression and antidepressant use during pregnancy while adjusting for the postnatal environment. One promising strategy is to use results from basic science to guide the inclusion of potential biological intermediates in advanced epidemiological studies.