Platelets and coagulation system play a pivotal part in the progression of peripheral arterial disease (PAD) and the genesis of complications. Therefore, antiplatelet and antithrombotic drugs represent one of the basic options for prevention and the treatment in such patients. As the data on the efficacy of these drugs in PAD patients are limited and contradictory, authors prepared an overview of the literature and recommendations for the use of these drugs. Antiplatelet therapy significantly reduces the incidence of death and cardiovascular events and prevents progression of local disease in PAD patients. Aspirin represents the first-line of antiplatelet drugs. Low-dose aspirin (75-325 mg) is as effective as higher doses. However, higher doses of aspirin result in increased risk of gastrointestinal (GI) bleeding and very low-doses (<75 mg) are less effective. Clopidogrel is used in place of low-dose aspirin in patients who have aspirin-related intolerance or allergy. Combined antiplatelet therapy is slightly more effective than aspirin alone only in patients with a history of established vascular disease. Oral anticoagulant therapy alone or in combination with aspirin was in PAD patients not shown to be more effective than aspirin alone in prevention of cardiovascular events, but is probably more effective in prevention of graft occlusion. However the combination is related to an increased risk of bleeding. Moderate intensity of warfarin treatment would be acceptable in the presence of coexisting indications such as atrial fibrillation or recent venous thrombosis.