A variety of pharmacologically different nonantidepressant agents have been studied for their ability to augment the efficacy of antidepressants in depressed patients who do not respond sufficiently. Among the strategies reviewed in this chapter, augmentation with lithium is the best-evidenced, showing clear efficacy in a metaanalysis of 10 placebo-controlled trials. All other commonly used augmentation strategies described in this chapter are not well supported by sufficient data from randomised controlled trials (RCTs). There is also a lack of controlled comparator studies with different augmentation agents. Such studies are needed to better guide physicians in the treatment of nonresponders to standard antidepressants.