In the past 2 decades, significant progress has been made in cardiovascular therapeutics. Effective drug therapies have been developed for hypertension, hypercholesterolemia, coronary artery disease, myocardial infarction, and congestive heart failure. Novel therapeutic strategies to treat cardiovascular disease consist of 3 major approaches: (1) changing the biology of vascular disease; (2) intervening in the ischemic event; or (3) modifying the post-ischemic course. The development of future therapies depends on continuing advancements in our understanding of the molecular mechanisms of vascular pathobiology. Novel therapies are aimed at the critical steps in vascular disease progression, which include reversing endothelial cell dysfunction, modulating thrombosis and inflammation, correcting dysregulated cell growth and apoptosis, modulating vascular phenotype, and modifying mechanicotransduction in vascular remodeling. Targeting these steps at the molecular level will stimulate the development of numerous therapeutic agents. Ongoing research will further define the role of the agents in the treatment of cardiovascular disease.