With the development and clinical implementation of the new cyclooxygenase (COX)-2 inhibitors, their safety, including the effects on renal function and blood pressure, is attracting increasing attention. In the kidney, COX-2 is constitutively expressed and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in mediation of renin release, regulation of sodium excretion, and maintenance of renal blood flow. Similar to conventional nonsteroidal anti-inflammatory drugs, inhibition of COX-2 may cause modest elevations in blood pressure in a minority of subjects. COX-2 inhibitors may also exacerbate pre-existing hypertension or interfere with other antihypertensive drugs. Special caution should be taken in patients with volume depletion or decreased organ perfusion.