Antidepressants are the most prescribed therapy for depression. The exact mechanism of action of antidepressants is unknown. The prevailing theory is that antidepressants increase the concentration of one or more brain chemicals (neurotransmitters) that nerves in the brain use to communicate with one another. The neurotransmitters affected by antidepressants are norepinephrine, serotonin, and dopamine. The different classes of antidepressants differ in the neurotransmitters they affect. This determines some of their side effects and potential drug interactions. All available antidepressants are effective, and for most cases of depression there is no good evidence that any antidepressant is more effective than another. Side effects and potential drug interactions are major factors that influence selection of antidepressants and compliance with therapy. This article discusses side effects and potential drug interactions of the major antidepressant classes.