Major depressive disorder (MDD) and bipolar disorder (BD) are principal psychiatric conditions affecting millions of people worldwide. These disorders present in myriad ways, and their management is challenging since there are so many variables that impact diagnosis and treatment. As yet there are no validated biomarkers in clinical use, and the psychiatrist has to rely entirely on history and mental state examination to make a tentative diagnosis and institute treatment measures in an empirical manner. There are subtle differences between MDD and BD, and discerning between the two is often difficult, such that misdiagnosis is common. Consequently, patients are treated inappropriately, which leads to worsening of the diathesis. The psychiatrist should be conversant with the current state of knowledge regarding the etiology, pathophysiology, and treatment of major mood disorders since these are the most common of all psychiatric conditions. In this chapter, principal mood disorders are comprehensively discussed in order to develop a better understanding of the two conditions. The emphasis is on recent developments in the field and an up-to-date knowledge base guides physicians in the management of mood disorders. To achieve this objective, literature published in the last 10 years is discussed and pertinent references are given for further appraisal. It is hoped that this chapter will be useful for all professionals who are involved in the care of patients with mental disorders.