Calciphylaxis is a devastating disorder with a mortality rate of 80% due to sepsis and organ failure. Hallmarks of this rare disease are arteriolar media calcification, thrombotic cutaneous ischemia, and necrotic ulcerations. Different mechanisms of vascular calcification can lead to calciphylaxis. Early diagnosis by deep cutaneous ulcer biopsy is most important for prognosis. Here, dermatologists play a significant role although treatment usually needs an interdisciplinary approach. Surgical procedures had been the cornerstone of treatment in the past including parathyroidectomy, but recently new medical treatments emerged aiming to normalize disturbances of minerals to reduce the serum concentration of sodium phosphate and to prevent precipitation and calcification. Multimodal therapy is warranted but only aggressive surgical debridement of cutaneous ulcers has shown significant outcome improvement.