Lower extremity peripheral artery disease (PAD) represents a significant public health problem, with its prevalence and association with cardiovascular morbidity and mortality as well as limb complications, resulting in reduced quality of life in affected individuals. Despite its burden and impact, PAD is underdiagnosed and undertreated compared to coronary artery disease and stroke, likely due to a general lack of awareness by the public and practitioners. In particular, the impact of PAD in low- and middle-income countries (LMICs) has been largely overlooked and is of particular concern given the increased burden of cardiovascular disease observed in LMICs in recent years. The aging of the global population, along with urbanization, industrialization, and increased prevalence of risk factors such as obesity, diabetes, and smoking have all contributed to the increasing burden of PAD in LMICs. This is of particular concern in settings where resources are limited and where early detection of PAD is crucial to implementing preventative interventions aimed at control of vascular risk factors, with the ultimate goal of improving cardiovascular and limb outcomes of this high-risk population. This chapter summarizes epidemiology, representative diagnostic tests, and major therapeutic challenges of PAD, with a special focus on resource-limited settings.