The efficacy of antidepressants has become a contentious topic over the last decade, and yet a review of the literature shows that they are consistently more effective than placebo. Although the average magnitude of this effect is unclear, many individual patients respond well to a course of antidepressants, and relapse when the medication is discontinued. Choosing the right antidepressant for a given patient remains more art than science, but the studies reviewed here provide some helpful guidance. Table 4 lists the second-generation antidepressants along with potential reasons for choosing one over the other (based on side effects, costs, or possible therapeutic advantages.) Based on these data, the following conclusions can be drawn: • For an all-around first-line antidepressant, sertraline is hard to beat, given its combination of efficacy, tolerability, and low expense. Once escitalopram becomes generic, it will join sertraline in this category. • Bupropion is often a first-line alternative to sertraline, because of its lack of sexual side effects; although it has less efficacy for anxiety disorders, it is helpful for other comorbidities, such as tobacco dependence and attention-deficit/ hyperactivity disorder. • Both paroxetine and mirtazepine are often maligned because of side effects of sedation and weight gain; however, these side effects may be advantageous for those whose depressive symptoms include insomnia and excessive weight loss. • Although not specifically reviewed in this article, certain antidepressants are liable to cause more drug–drug interactions than others; the most prominent of these are fluoxetine, paroxetine, and fluvoxamine.