Purpose of Review <p>Several psychobiological factors are supposed to play a role in the association between insomnia and mental disorders. The current review was aimed at providing an overview of the associations between brain-derived neurotrophic factor (BDNF), insomnia, and psychopathology.</p> Recent Findings <p>BDNF is involved in neural plasticity and supports cognitive functioning and mood regulation. In animal models, sleep deprivation produces a decrease in central (e.g., hypothalamic) BDNF. Peripheral BDNF is sensitive to sleep loss in animal and human studies, and serum BDNF concentrations are remarkably lower in individuals with persistent insomnia and patients with mental disorders compared to their respective healthy controls. Recent evidence suggests that both non-rapid-eye-movement (NREM) and REM sleep may be associated with BDNF.</p> Summary <p>Theoretical models and empirical data suggest that BDNF expression is reduced in patients with stress-related mood, anxiety, and psychotic disorders. Therefore, BDNF may play a critical role in the association between insomnia and psychopathology. Putatively, persistent sleep disruption may downregulate BDNF through several factors including neuroinflammation (e.g., cytokines, migroglia) and stress-related hormones (e.g., glucocorticoids) which may, in turn, increase the risk of psychopathology. Research on the effects of standard insomnia treatment on BDNF still needs to be developed. </p>