This column is the second in a series exploring drug-drug interactions (DDIs) with a special emphasis on psychiatric medications. The first column in this series discussed why patients being treated with psychiatric medications are at increased risk for taking multiple medications and thus experiencing DDIs and how to recognize such DDIs, and strategies for avoiding them. This second column in the series discusses strategies for minimizing adverse outcomes from such unintended DDIs. Given the huge and rapidly increasing number of available prescription and over-the-counter medications as well as nutritional supplements, the author recommends that all prescribers develop a personal formulary of ∼30 drugs that they use in everyday practice and with which they are intimately familiar. It is recommended that their knowledge of these drugs include both their generic and brand names (to avoid confusion leading to prescription of the wrong drugs), routinely used doses, pharmacokinetics including half-lives, pharmacodynamics including mechanism(s) of action and binding profile for specific receptors, adverse effect profiles, potential DDIs, and the evolving research literature on these agents. The author stresses the value of establishing a therapeutic alliance involving the patient and the people around him or her (eg, prescribers, family members, pharmacists, nurse practitioners, home health professionals, friends when appropriate) to promote the patient’s understanding of and adherence to treatment. It is also important to establish a therapeutic goal with a specific time expectation (eg, reduction in depressive symptoms within 4 wk), after which the prescriber should discuss adherence with the patient and significant others, consider a dose adjustment, or discontinue the drug after an adequate therapeutic trial or the development of an adverse effect that outweighs any benefit the drug may be having. The author outlines major principles for avoiding adverse DDIs and includes a table of online resources that provide information concerning different types of DDIs. The column ends with a discussion of limitations of currently available drug alert software programs and information on how and where to report adverse drug reactions.