This column begins a series exploring drug-drug interactions (DDIs) with a special emphasis on psychiatric medications. As explained in this column, this topic is important for multiple reasons. First, a large percentage of the population is receiving psychiatric medications. Second, these patients are likely to be on multiple medications which means that they are at risk for an adverse DDI. Third, DDIs may occur but not be recognized even though they have significant health care consequences for the patient. Fourth, these consequences can range from a catastrophic outcome to more everyday clinical problems involving a myriad of presentations as enumerated in this column. Also discussed in this column is the fact that all drugs, including psychiatric medications, interact on the basis of their pharmacodynamics and pharmacokinetics rather than their therapeutic use. Therefore, psychiatric medications may interact with medications prescribed for nonpsychiatric reasons as well as with other psychiatric medications. Tables are included that explain reasons for multiple medication use and principles to follow to minimize the risk of adverse DDIs.