Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used drugs with potential effects on systemic blood pressure. NSAIDs act by inhibiting synthesis of prostaglandins (PGs) from arachidonic acid via cyclooxygenase (COX)-1 and COX-2, the 2 isoforms of COX. NSAIDs may affect blood pressure via the renin-angiotensin pathway, alterations in sodium and water retention in the kidneys, inhibition of vasodilating PGs, and production of various vasoconstricting factors, including endothelin-1 and P450-mediated metabolites of arachidonic acid. In 2 meta-analyses, it was found that NSAIDs have small but significant effects on blood pressure, most notably in hypertensive patients on antihypertensive medication. NSAIDs cause small (<5 mm Hg) elevations in systolic blood pressure, and little or no change in diastolic blood pressure. The incidence rates of hypertension and peripheral edema were low, ranging from <1% to >9% of patients. The incidence and levels of hypertension associated with COX-2 inhibitors are within the range of those observed with nonspecific NSAIDs. Apparent differences between the COX-2 inhibitors celecoxib and rofecoxib may be functions of differences in study population susceptibilities to NSAID-mediated hypertensive effects. Patients at risk for hypertension should be monitored for changes in blood pressure during NSAID treatment.