Diabetes mellitus is a highly prevalent disease. Chronic kidney disease is one of its chronic complications, and diabetic ketoacidosis is one of the most dreaded acute complications. The increasing prevalence of diabetes mellitus and renal failure has resulted in physicians increasingly encountering diabetic ketoacidosis in this complicated subgroup of patients. This review discusses the pathophysiologic understanding of diabetic ketoacidosis in patients with renal failure, its varying clinical presentation, and management and prevention. We have also highlighted the role of patient weight and proximity to dialysis as tools to assess and manage fluid status in this challenging group of patients.