Major depressive disorder (MDD) is a prevalent disorder that is also highly comorbid with other psychiatric and medical conditions. After diagnosing a major depressive episode, clinicians should screen for suicide risk to establish patient safety. Once the patient is in the appropriate treatment setting, clinicians should evaluate the patient for MDD by assessing the differential diagnosis, accompanying symptoms, psychiatric and medical comorbidities, and sociodemographic factors. Proper assessment of patients with MDD can lead to targeted treatment and a better chance of remission.