Central serotonergic signaling influences many physiological processes, but a requirement for reproductive success has not been demonstrated. Using mouse dams with a specific disruption in serotonin neuron development, we found that serotonergic function is required for the nurturing and survival of offspring. Full rescue of survival depended on the mother's expression level of the upstream serotonergic transcriptional cascade. Thus, intrinsic transcriptional programming of maternal serotonergic activity determines the quality of nurturing and whether or not the organism survives.