A key objective in the field of translational psychiatry over the past few decades has been to identify brain biomarkers of major depressive disorder (MDD) to support the development of more effective interventions. Considerable progress has been made toward this aim; however, despite its initial promise, neuroimaging has not been widely translated into clinical practice. Various barriers have impeded the detection of clinically relevant neuroimaging markers, including (1) many studies have been conducted with small samples, which has led to a lack of reproducible findings; (2) advances in understanding the pathophysiology of depression have been made at a group level, lacking predictive value at the individual patient level; and (3) most studies have not evaluated the predictive value of potential neuroimaging biomarkers for future clinical outcomes.