The diversity of antidepressant mechanisms available today allows clinicians to individualize treatment decisions for depressive symptoms and subtypes, as well as to avoid side effects. The mechanism of action of antidepressants allows prediction of both adverse effects and therapeutic effects. Individual antidepressants have unique psychopharmacologic profiles, and individual patients have unique clinical profiles of different symptoms and depressive subtypes. By using this knowledge, the prescriber can match drug profiles with patient profiles to select preferred agents and avoid less preferred agents.