In the clinical management of heart disease, calcium channel blockers are generally prescribed in combination with one or more anti-angina, antiarrhythmic, or antihypertensive agents. Two different mechanisms are involved in drug interactions: pharmacokinetic and pharmacodynamic. In the former, the disposition of one drug is altered by the action of another, causing an increase or decrease in its absorption or its modified distribution, metabolism, or excretion. In pharmacodynamic interactions, the physiologic effects of one drug interfere either directly or indirectly with those of another, for instance, by alterations in fluid or electrolyte balance. This effect may be antagonistic or additive. The present work outlines the possible adverse interactions between the three main calcium antagonists and other therapeutic agents, including digoxin, beta blockers and antiarrhythmic, anesthetic, antihypertensive, antiasthmatic, and antidiabetic drugs and contrast media. Knowledge of these effects is of major clinical importance in the treatment of cardiac patients.