Structural abnormalities are demonstrated in various neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, and even major depression. On the other hand, recent studies have demonstrated the structural and functional modifications in the adult brain that are associated with synaptic plasticity and neurogenesis. Accordingly, regulation of synaptic plasticity and neurogenesis may lead to the development of novel treatments for neuropsychiatric disorders. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) have important roles not only in neuronal survival and differentiation, but also in the formation and maintenance of neural circuits and synapse plasticity. Accumulating evidence suggests that these neurotrophic factors may be applied to the treatment of neuropsychiatric disorders. In addition, compounds that increase the expression of BDNF and/or GDNF in the brain should have potential therapeutic values. We have demonstrated that systemic administration of dipeptide Leu-Ile increases BDNF and GDNF production in the brain, and has a protective role in methamphetamine and morphine dependence. In this review, we discuss the potential role of BDNF, GDNF and their inducers in the treatment for neuropsychiatric disorders.