Mood disorders, such as major depressive disorder and bipolar disorder, are common, severe and chronic psychiatric diseases. There is an increasing recognition that the pathophysiology of mood disorders could be the result of dysregulation of synaptic plasticity with alterations in the levels of neurotrophins. Brain-derived neurotrophic factor (BDNF), the most abundant neurotrophin in the brain, has been investigated extensively in mood disorder. BDNF is important for neuronal growth, development, differentiation and survival. In addition, BDNF can modulate synaptic plasticity and its molecular mediators across multiple neurotransmitter systems, as well as the intracellular signal-transduction pathway. From findings in animal as well as clinical studies, the BDNF gene is considered an attractive candidate for predicting mood disorders or antidepressant/mood stabilizer therapeutic response. In this review, we summarize the findings of recent investigations of the effects of the BDNF gene on therapeutic response and the risk for mood disorders. Although the general conclusion to be drawn from the findings of these genetic studies, is that BDNF genetic variants have implications for the pathogenesis and treatment of mood disorders, the findings of these studies are sometimes inconsistent. Several recommendations are proposed for future genetic studies of BDNF signaling pathways in mood disorders.