<p>Lithium has been the treatment of choice for bipolar disorder for many years. The element, in its ionic form, was first shown to have medical applications in the 1840s for the treatment of bladder stones and gout. However, it was not until the late 19th century that the therapeutic effects of lithium in bipolar disorder became recognized and its use re-established and made mainstream by John Cade in 1949. A significant amount of credit is attributed to Mogens Schou, who did the first series of systematic trials with bipolar disorder patients during the 1950s and 1960s and proved the short-term and prophylactic efficacy of lithium. Since these discoveries, lithium has been widely prescribed in the treatment of bipolar disorder and the trends continued based on the high success rate with approximately 70% to 80% of patients showing full or partial response. Lithium works particularly well with bipolar disorder as it has been shown efficient both as a prophylactic and as a mood stabilizer in episodic treatment, thus addressing the dual nature of the disease. Given the debilitating nature of bipolar disorder, its lifetime prevalence, and significant occurrence in the general population (1% to 2%), understanding the mode of action of its most efficient line of treatment is an essential endeavor. </p> <h4>ABOUT THE AUTHORS</h4> <p>Cristiana Cruceanu, BSc; Catalina Lopez de Lara, MD; and Gustavo Turecki, MD, PhD, are with the Department of Psychiatry, Douglas Hospital, McGill University, Montreal, Quebec, Canada. Martin Alda, MD, is with the Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. </p> <p>Address correspondence to: Gustavo Turecki, MD, PhD, William Dawson Chair, Douglas Hospital, McGill University, 6875 LaSalle Blvd., Verdun, QC H4H 1R3, Canada; or e-mail <a href="mailto:gustavo.turecki@mcgill.ca" target="_new">gustavo.turecki@mcgill.ca</a>. </p> <p>Dr. Cruceanu, Dr. Lopez de Lara, Dr. Turecki, and Dr. Alda have reported no relevant financial relationships.</p> <h4>EDUCATIONAL OBJECTIVES</h4> <ol><li>Demonstrate that lithium response aggregates in families, underscoring the importance of family history of therapeutic response in optimal selection of mood stabilizing pharmacotherapy.</li> <li>Describe the clinical characteristics (episodic course of illness with complete recovery; no rapid cycling), which may predict a good therapeutic response to lithium </li> <li>Discuss that no specific genes have yet been associated unequivocally with lithium response. </li></ol>