Current evidence indicates that selective COX-2 inhibitors have important adverse cardiovascular effects that include increased risk for myocardial infarction, stroke, heart failure, and hypertension. The risk for these adverse effects is likely greatest in patients with a prior history of or at high risk for cardiovascular disease. In these patients, use of COX-2 inhibitors for pain relief should be limited to patients for whom there are no appropriate alternatives, and then, only in the lowest dose and for the shortest duration necessary. More long-term data are needed to fully evaluate the extent to which these important adverse cardiovascular effects may be offset by other beneficial effects of these medications. More data are also needed on the cardiovascular safety of conventional NSAIDs. Until such data are available, the use of any COX inhibitor, including over-the-counter NSAIDs, for long periods of time should only be considered in consultation with a physician. The debate about the increased risk of cardiovascular events attributed to the selective COX-2 inhibitors and the nonselective NSAIDs is part of a broader national debate about drug safety. Optimal safety evaluation of drugs requires timely and complete submission of scientific data from the manufacturers, as well as increased funding and authority granted to the FDA by Congress. © 2007 American Heart Association, Inc.