Salicylates are effective prophylactic treatment strategies for myocardial infarction and ischemic strokes. Recent evidence suggests that high doses of salicylates may exert direct, platelet-independent effects on the vascular wall. Salicylate and aspirin, in concentrations between 1 and 5 mM, effectively inhibit vascular smooth muscle cell proliferation and DNA synthesis without inducing cellular toxicity or apoptosis. This inhibition is associated with effects on specific cell-cycle regulatory molecules, and may proceed via downregulation of the transcription factor, nuclear factor (NF)-kappaB. High-dose salicylates and selective NF-kappaB inhibitors may, therefore, play an important role in the management of vascular proliferative disorders.