Burden of psychiatric disorders is compounded by their wide prevalence as well as the limited efficacy of currently available treatments and the current approaches for prescribing these treatments. The selection of treatments continues to be subjective and often results in a trial-and-error approach. Emerging research suggests that biological markers (or biomarkers) can be used to develop precision medicine approaches for psychiatric disorders. Furthermore, the biomarkers also promise to elucidate the underlying pathophysiological mechanisms which in turn can be used to develop novel therapeutic treatments. In this chapter we have focused on mood disorders and reviewed studies on electroencephalography (EEG), magnetic resonance imaging (MRI), and blood-based biomarkers that can guide selection of one treatment versus another (treatment-selection biomarker) as well as biomarkers that can guide the development of novel therapeutics. These studies suggest that the use of objective physiological data is poised to alter the landscape of psychiatric diagnosis and treatment. However, practical and economic barriers remain as major hurdles. The key to finding such translational diagnostic and therapeutic biomarkers is a better understanding of the underlying pathophysiology, and despite the tremendous advances in neuroscience, it is clear there remains much left to be elucidated.