Peripheral artery disease (PAD) represents a major health care burden. Despite the advent of screening and interventional procedures, the long-term clinical outcomes remain suboptimal, especially in patients with chronic kidney disease (CKD). While CKD and PAD share common predisposing factors, emerging studies indicate that their co-existence is not merely an association; instead, CKD represents a strong, independent risk factor for PAD. These findings implicate CKD-specific mediators of PAD that remain incompletely understood. Moreover, there is a need to understand the mechanisms underlying poor outcomes after interventions for PAD in CKD. This review discusses unique clinical aspects of PAD in patients with CKD, including high prevalence and worse outcomes after vascular interventions and the influence of renal allograft transplantation. In doing so, it also highlights underappreciated aspects of PAD in patients with CKD, such as disparities in revascularization and higher peri-procedural mortality. While previous reviews have discussed general mechanisms of PAD pathogenesis, focusing on PAD in CKD, this review underscores a need to probe for CKD-specific pathogenic pathways that may unravel novel biomarkers and therapeutic targets in PAD and ultimately improve the risk stratification and management of patients with CKD and PAD.