Introduction: Chronic limb ischemia (CLI) and diabetic foot significantly impact patients’ quality of life, with high rates of amputation and mortality. Angiosome-oriented revascularization represents an anatomically precise approach, targeting the artery that directly supplies the lesion area. Direct revascularization (DR) is increasingly considered superior to indirect revascularization (IR) due to potentially better wound healing and limb salvage outcomes. Methods: A narrative literature review was conducted using PubMed, Cochrane Library, and Google Scholar, with the keywords: angiosome, critical limb ischemia, diabetic foot, direct revascularization, endovascular, bypass surgery. Studies published between 2020 and 2025 were included, focusing on systematic reviews, meta-analyses, and prospective cohort and clinical studies. In addition to clinical studies, anatomical data on the distribution of foot and lower leg angiosomes were analyzed, including a table illustrating the correlation between wound location and target artery. Results: Six main angiosomes of the lower limb were identified, each corresponding to a specific artery. DR was associated with higher rates of wound healing and limb preservation, reducing the risk of amputation by 20–30% compared to IR. Optimal candidates for DR are those with localized lesions, patent distal target arteries, and adequate microcirculation. DR is less effective or technically unfeasible in patients with diffuse microvascular disease, multisegment occlusions, poor distal vessels, or active severe infections. Advanced technologies such as hyperspectral imaging and indocyanine green (ICG) mapping improve intraoperative perfusion assessment. Conclusion: Angiosome-oriented revascularization is a logical and anatomically grounded approach for treating CLI and diabetic foot. When feasible, DR of the target artery provides better clinical outcomes than IR. Success requires precise diagnostics, patient selection, and multidisciplinary collaboration. Further randomized studies are needed to define optimal application algorithms for this concept.

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