It is now clear that different pathophysiologic mechanisms have a profound influence on the extent of the functional impairment in intermittent claudication. In particular, metabolic derangements, including impaired oxygen delivery and/or extraction, reduced nitric oxide synthesis, reduced glucose oxidation, accumulation of toxic metabolites and reduction in carnitine availability are correlated with disease severity. Therefore, metabolic interventions aimed at counteracting these alterations may represent a valid therapeutic approach to the treatment of this condition. To date, verapamil and L-arginine efficacy has been proven in few patients; a large scale clinical trial, conversely, reports that propionyl-L-carnitine appears to be an effective and well tolerated drug for the treatment of intermittent claudication.