Interactions among drugs and non-drug substances are the bane of all therapeutic and adverse endpoints in clinical practice. Alterations in drug absorption, distribution, metabolism, and excretion often characterize pharmacokinetic interactions. The drug targets (e.g., transporter, receptor, enzyme, microbiota) that contribute to the overall outcome or effects (e.g., secretions, blood clotting, blood pressure, plasma electrolyte concentration) are important components of pharmacodynamic interactions. This chapter explores the mechanism of interactions and the risk of undesirable effects. Pharmacokinetics and pharmacodynamics research could elucidate the underlying mechanisms of drug interactions, develop predictive models for identifying potential interactions, and discover new strategies for minimizing the risk of adverse effects.