Increasing number of studies has during the last decade linked neurotrophic factors with the pathophysiology of neuropsychiatric disorders and with the mechanisms of action of drugs used for the treatment of these disorders. In particular, brain-derived neurotrophic factor BDNF and its receptor TrkB have been connected with the pathophysiology in mood disorders, and there is strong evidence that BDNF signaling is critically involved in the recovery from depression with both pharmacological and psychological means. Neurotrophins play a central role in neuronal plasticity and network connectivity in developing adult brain, and recent evidence links plasticity and network rewiring with mood disorders and their treatment. Therefore, neurotrophins should not be seen as happiness factors but as critical tools in the process where brain networks are optimally tuned to environment, and it is against this background that the effects of neurotrophins on neuropsychiatric disorders should be looked at.