Diabetes mellitus and peripheral artery disease are prevalent diseases throughout the world and often present simultaneously in the same patient, which has direct implications for their diagnosis and management. Refinements of existing and development of new diagnostic and treatment modalities are changing the management of these diseases. This article reviews the significant pathologic basis, history, and physical examination findings with respect to each disease and their presentation together. Advantages and disadvantages of different diagnostic modalities, including noninvasive studies and imaging technologies, are discussed. General medical management principles and indications, techniques, and efficacy of surgical and endovascular interventions are reviewed.