Preeclampsia affects 2–7% of pregnancies and is a leading cause of maternal and fetal morbidity and mortality. Despite extensive study, the etiology of preeclampsia is poorly understood. Abnormal placental development, predisposing maternal constitutional factors, oxidative stress, immune maladaptation, and genetic susceptibility have all been hypothesized to contribute to the development of preeclampsia. Physical conditioning and preeclampsia have opposite effects on critical physiological functions. This suggests that regular prenatal exercise may prevent or oppose the progression of the disease. Epidemiologic studies show that occupational and leisure-time physical activity is associated with a reduced incidence of preeclampsia. We hypothesize that this protective effect results from one of more of the following mechanisms: 1) stimulation of placental growth and vascularity, 2) reduction of oxidative stress, and 3) exercise-induced reversal of maternal endothelial dysfunction. Future research should include prospective epidemiological case-control studies that accurately measure occupational and leisure-time physical activity. Controlled randomized clinical trials examining the effects of prenatal exercise on biochemical markers for endothelial dysfunction, placental dysfunction, and oxidative stress are also needed. If future research supports the idea that exercise effectively protects against preeclampsia, this would provide a low-cost intervention that could dramatically improve prenatal care for women at risk of this disease.