Calciphylaxis is a rare, progressive disorder characterized by subcutaneous adipose and dermal microvascular calcifications, microthrombi, and endothelial damage. It mainly affects patients with chronic kidney disease (CKD), which is also known as calcific uremic arteriolopathy. Skin biopsy is the gold standard for diagnosis, but it is an invasive procedure. Calciphylaxis frequently results in ischemic and nonhealing ulcerations with a high mortality rate. A multidisciplinary targeted approach is the primary treatment method. Vascular calcification, which is a common complication in patients with CKD, cannot completely explain the rapid progression of calciphylaxis. This article reviews the advances in the epidemiological characteristics, risk factors, and diagnosis, including non-uremic calciphylaxis and visceral calciphylaxis, pathogenesis, associated animal models, and treatment of calciphylaxis. The scarcity of animal models that mimic the clinical presentation of calciphylaxis hampers the understanding of its pathogenesis. The acute effects on progressive vascular injury, including the induction of severe ischemia and inflammatory responses, have been emphasized. Actively listening to the voices of patients and their families and building a multidimensional research system with artificial intelligence technologies based on the specific molecular makeup of calciphylaxis patients will help tailor regenerative treatment strategies. Mesenchymal stem cells (MSCs) may represent a novel therapy for calciphylaxis because of their regenerative effects, inhibition of vascular calcification, anti-infection and immunomodulation properties, and improvement of hypercoagulability. Safe, effective, accessible, and economical MSC strategies guided by biomarkers deserve consideration for the treatment of this devastating disease.