Despite growing evidence that increased brain-derived neurotrophic factor (BDNF) and hippocampal adult neurogenesis are necessary for the behavioral actions of antidepressants in rodents, the cellular mechanisms involved in these effects are still unknown. Li et al. in this issue of Neuron demonstrate that the presence of TrkB, the high-affinity receptor for BDNF, in hippocampal neural progenitor cells is required for the neurogenic and behavioral actions of antidepressant treatments.