Systemic atherosclerosis and its risk factors are present in the majority of patients with critical limb ischemia. Aggressive medical therapy is an immediate and necessary part of the work-up and management of these patients and will involve a multidisciplinary approach. Risk stratification based on a patient's current clinical cardiovascular condition is important in determining the most appropriate and safe intervention and will allow both the patient and physician to make an informed decision regarding risk- and cost-benefits of treatment.