Calciphylaxis is a rare painful skin condition classically seen in patients with end-stage renal disease (ESRD), particularly those on chronic dialysis; however, it also has been increasingly reported in patients with normal renal function. Calciphylaxis is associated with high mortality rates, and excruciating pain and nonhealing ulcers often lead to recurrent hospitalizations and infectious complications. It is critical for dermatologists to recognize the clinical features of calciphylaxis to ensure accurate and timely diagnosis and proper management. In this article, we provide an update on calciphylaxis etiopathogenesis, diagnosis, and management, and we highlight the challenges faced in managing this potentially fatal condition.