Calcific uremic arteriolopathy (CUA) is a rare but serious complication of end-stage renal disease presenting as painful cutaneous lesions and progressing to non-healing ulcers and gangrene. This syndrome is associated with calcium and phosphorus deposits within small arteries of the skin. The pathognomonic lesion is vascular calcification with intimal arterial hypertrophy and superimposed small-vessel thrombosis. The condition is being increasingly recognized and reported as a contributing factor to death in dialysis patients, with secondary infection and sepsis as the major cause of mortality. No standard treatment has been established for this syndrome. We present the therapeutic approach employed in two patients, which successfully resulted in healing of the lesions, using a combination of measures to control the factors potentially related to development of CUA and hyperbaric oxygen therapy.