Antidepressants are the subject of lively public debate. Over one million Dutch people are prescribed an antidepressant each year for a variety of reasons. The number of long-term antidepressant users is smaller, estimated to be around 150,000 patients for over a year for depression. Clinicians and patients together must carefully weigh the pros and cons of antidepressants. In this article, we discuss the latest scientific insights how antidepressants can be used rationally.