There is a paucity of trials that specifically evaluate the benefits of cardiovascular risk reduction therapies in patients with peripheral arterial disease. We therefore sought to describe the data supporting the use of therapies for lowering cardiovascular risk, preventing ischemic events, as well as managing intermittent claudication, in these patients. A search for randomized, placebo-controlled trials in peripheral arterial disease was conducted using Medline and reference lists of relevant articles. These trials served as the primary sources of data and treatment recommendations, while observational studies and case series were included as sources of commonly accepted treatment recommendations that were not fully supported by the randomized trial. Data from the primary sources support the use of antiplatelet therapy and, potentially, of angiotensin-converting enzyme inhibitors, for preventing ischemic events. In contrast, the evidence demonstrates a nonsignificant trend for treating dyslipidemia to prevent mortality and does not specifically support intensive glycemic control in persons with diabetes or estrogen use in these patients. However, observational data and data derived from trials in persons with other manifestations of cardiovascular disease may be generalized to support the importance of treating key risk factors, such as smoking, diabetes, dyslipidemia, and hypertension. Data supporting the use of estrogen to reduce cardiovascular risk are less clear. Studies do demonstrate improvement in walking ability resulting from exercise rehabilitation programs, as well as from use of cilostazol and, to a more modest degree, pentoxifylline. The consensus is to treat risk factors of peripheral arterial disease patients similarly to patients with other manifestations of atherosclerosis and to use exercise rehabilitation or cilostazol to treat the subset of patients with claudication.