Treatment of critically ill patients with continuous renal replacement therapy (CRRT) requires a set of new skills and knowledge base for the intensive care unit (ICU) nurse. After a decision to treat is made, nurses effectively manage the technique by following a series of steps in sequence. These sequential steps include patient and machine circuit preparation, connection of the extracorporeal circuit (EC) to the patient's vascular access, and nursing management of a treatment in progress. During treatment, nurses prepare fluids, adjust fluid settings to provide fluid balance, prepare electrolyte additives, monitor acid base and electrolyte levels, monitor patient and machine "vital signs," and, when necessary, diagnose circuit clotting and perform a disconnection of the EC from the patient. All of these aspects of CRRT nursing are essential for a successful CRRT nursing policy or protocol. This chapter provides a clinical review for this every day sequence when using CRRT in the ICU setting.