Drugs that inhibit platelet activation may prevent thrombosis and atherosclerosis. The mechanism by which coumarins, heparin, calmodulin inhibitors, calcium entry blockers, drugs that interfere with cyclic AMP function and arachidonate metabolism, and several other compounds might achieve this protection, is discussed. Only a few of these drugs (acetylsalicylic acid, dipyridamole, sulfinpyrazone) have been tested for clinical efficacy in man. So far the results of these studies have revealed modest protection from infarction and other cardiovascular diseases.