Continuous renal replacement therapy (CRRT) is commonly applied in critically ill patients affected by severe acute kidney injury for solute and volume control and to optimize acid-base and electrolytes balance. Although CRRT represents a life-saving procedure for these patients, it is a representation of a non-physiologic artificial kidney and the potential benefits of the treatment could be hampered by clinical and technical side effects. Different parts of the CRRT system can be a source of technical complications. Vascular access dysfunction, activation of the coagulation system, air embolism, heat loss and hypothermia, fluid balance errors, and immune system activation are some issues the medical and nurse staff have to face daily in patients undergoing CRRT. A detailed understanding of these complications and knowledge about the technology that the staff are dealing with are fundamental aspects for applying CRRT safely and efficaciously.