Lower-extremity peripheral arterial disease (PAD) is defined as atherosclerotic disease that affects the arteries supplying the legs. While it is age-related, PAD has shown to have a large prevalence globally and continues to be an increasingly serious public health problem, especially in low-income and middle-income countries. Reported data regarding the prevalence and incidence of PAD might vary according to the diagnostic criteria used to define PAD. While PAD is overall not considered by physicians to be as equally important as other manifestations of cardiovascular disease, recent evidence also demonstrates an overwhelming lack of awareness of PAD among the public. Traditional risk factors include age, smoking, hypertension, dyslipidemia, and diabetes. Among these factors, the risk of developing PAD is best predicted by the presence of cigarette smoking and diabetes. This underscores the importance of lifestyle modifications including smoking secession; blood pressure, lipid, and glucose control; and promotion of physical activity and healthy diet, as well as awareness, in management of PAD. In recent years, particular interest in novel biomarkers has led to studies on the role of inflammation and hemostasis, homocysteine, and environmental hazards, among others, in peripheral atherogenesis. Results regarding the genetic variants in association with PAD remain inconclusive. PAD is likely a complex disorder resulting from interplay between multiple different genes, with modest effect sizes, and the environment stimuli. While differences in PAD symptoms and presentation have been observed between women and men, important gaps in knowledge regarding sex-specific and gender-related aspects in PAD remain.