Drug-drug interactions (DDIs) are a critical issue within clinical practice, particularly in psychiatric settings. DDIs pose significant risks to patient safety, requiring clinicians to have a thorough understanding of pharmacology, particularly the P450 enzyme system and its genetic variations among individuals. The chapter emphasizes the importance of recognizing potential interactions and utilizing resources such as drug interaction databases to manage and mitigate risks. A case study is presented involving a 93-year-old woman experiencing recurrent syncopal episodes linked to the concurrent use of metoprolol and diphenhydramine, medications that interact via the same metabolic pathway. The case highlights the necessity of evaluating patients for high-risk factors for ADEs, such as age, polypharmacy, and genetic differences in drug metabolism. Strategies for preventing DDIs include taking comprehensive medication histories, identifying patients at risk, and utilizing references for pharmacogenetics to tailor treatment approaches. Additionally, the use of potentially inappropriate medications in older patients remains a pressing concern, as it increases risks of DDIs and adverse events.