The incidence and severity of drug interactions are on the rise as more medications are brought to market. Following the absorption, distribution, metabolism, and excretion model of pharmacokinetics, this review will provide an overview of the varied mechanisms of drug-drug, drug-herb, and drug-food interactions with emphasis placed on the interactions most likely to cause harm. This information is intended to assist the pediatric emergency physician in recognizing drug interactions to identify and remove the offending agent when appropriate. Understanding the mechanisms of drug interactions will assist all clinicians in avoiding these serious, often preventable, events.