Continuous renal replacement therapy (CRRT) has many potential indications that extend beyond the traditional removal of uremic waste products. Many of these stem from the capacity of CRRT to remove middle-sized molecules and its suitability for haemodynamically unstable patients. Using CRRT for immunomodulation to remove circulating plasma cytokines has created great enthusiasm and, in the past, immunomodulation was a frequently reported indication for commencing CRRT. Unfortunately, recent evidence from randomized controlled trials has been discouraging, and CRRT cannot be recommended for immunomodulation. The contemporary indications of CRRT include fluid removal in fluid overloaded patients with poor tolerance of volume load when other means of fluid removal are insufficient or have failed; removal of toxins such as ammonia and myoglobin, as well as acidosis management in metformin-associated lactic acidosis when severe acid-base disorders coexist. Other potential indications include removal of ingested toxins and tumour lysis syndrome in severely unstable critically ill patients.