Significant drug interactions contribute to hospitalizations, mortality, and health care costs. They often are preventable with a basic understanding of pharmacokinetics and pharmacodynamics. More than quarter of Americans above the age of 40 years take a statin, the most commonly used lipid-lowering therapy in modern times. Because of their pharmacokinetics, statins interact with numerous other drugs and substances, often in a manner that differs from statin to statin. This article provides an overview of important drug interactions for the most commonly used medications in preventive cardiology, with an emphasis on clinically significant interactions involving statins.