Bipolar disorder (BD) is a persistent psychiatric condition characterized by severe fluctuations in mood, energy levels, and activity levels. Despite extensive study, the exact neurobiological mechanisms underlying BD remain elusive. Multiple lines of evidence suggest that alterations in brain-derived neurotrophic factor (BDNF) contribute to the development of BD and impact the efficacy of mood stabilizers. Furthermore, the anesthetic ketamine, along with its enantiomers, has demonstrated rapid-acting antidepressant and anti-suicidal effects in individuals suffering from bipolar depression. In this chapter, the author provides a succinct overview of the history of BDNF, outlines the process of mature BDNF from its precursor, and explores the possible roles of BDNF, its precursor proBDNF, and long non-coding RNAs that can modulate BDNF expression, in serving as potential biomarkers for BD.