Brain-derived neurotrophic factor (BDNF) has a primary role in neuronal development, differentiation and plasticity in both the developing and adult brain. A single-nucleotide polymorphism in the proregion of BDNF, termed the Val66Met polymorphism, results in deficient subcellular translocation and activity-dependent secretion of BDNF, and has been associated with impaired neurocognitive function in healthy adults and in the incidence and clinical features of several psychiatric disorders. Research investigating the Val66Met polymorphism has increased markedly in the past decade, and a gap in integration exists between and within academic subfields interested in the effects of this variant. Here we comprehensively review the role and relevance of the Val66Met polymorphism in psychiatric disorders, with emphasis on suicidal behavior and anxiety, eating, mood and psychotic disorders. The cognitive and molecular neuroscience of the Val66Met polymorphism is also concisely reviewed to illustrate the effects of this genetic variant in healthy controls, and is complemented by a commentary on the behavioral neuroscience of BDNF and the Val66Met polymorphism where relevant to specific disorders. Lastly, a number of controversies and unresolved issues, including small effect sizes, sampling of allele inheritance but not genotype and putative ethnicity-specific effects of the Val66Met polymorphism, are also discussed to direct future research.