Relationship between neurotrophins, especially brain-derived neurotrophic factor (BDNF) and bipolar disorder (BPD) has been widely investigated, but results have been inconsistent. BDNF polymorphism may be associated with the susceptibility to subtype BPD such as rapid cycling BPD or early onset BPD. Met allele carriers of Val66Met of BDNF gene had smaller gray matter (GM) in both patients and healthy controls, but bipolar patients carrying Met allele had better response to lithium treatment. Decreased serum/plasma BDNF levels were observed at different mood states. BDNF may interact with other systems to execute its neuroprotective effects. Overall data suggest that neurotrophins may be involved in the pathogenesis of BPD and treatment response, but the magnitude of their role needs further investigation with large sample size studies.