Data from livestock species and experimental animal models suggest that excess body fatness may impair lactogenesis. For example, it has long been known that overfed dairy cows are at risk of fat cow syndrome, a condition characterized by lactation failure in the early postpartum period. Obese rats often lose their litters in the early postpartum period to primary lactation failure. A negative association between high body mass index (BMI) before conception and the duration of lactation has been documented in studies from diverse human populations. Findings from our laboratory establish that among women who ever attempted to breastfeed their infants, high BMI before conception was also associated with failure to initiate breastfeeding successfully. In a more recent study, we found that high prepregnant BMI was specifically associated with later onset of lactogenesis II. This was mediated by parity but not by breastfeeding behavior. Psychosocial factors related to a woman's intention to breastfeed and her planned duration of breastfeeding did not modify this association. Taken together, these findings in animals and women strongly suggest that maternal obesity in the perinatal period is a cause of delayed lactogenesis.