Major depressive disorder and bipolar disorder are highly prevalent (Kessler et al. 2003, 2005) and are among the top 10 causes of disability worldwide (Murray and Lopez 1996). These mood disorders tend to be underrecognized and undertreated (Kessler et al. 2003; Wang et al. 2005), despite substantial evidence that supports the efficacy and effectiveness of pharmacological and psychotherapeutic interventions. In this chapter we critically review the available evidence for the efficacy and adverse effects of antidepressant and antimanic medications as well as evidence for the management of treatment-resistant mood disorders. To the greatest extent possible, only controlled trials of adequate size will be used to make treatment recommendations.