Emerging evidence from observational studies suggests that both slower and faster net ultrafiltration rates during kidney replacement therapy are associated with increased mortality in critically ill patients with acute kidney injury and fluid overload. Faster rates are associated with ischemic organ injury. The net ultrafiltration rate should be prescribed based on patient body weight in milliliters per kilogram per hour, with close monitoring of patient hemodynamics and fluid balance. Randomized trials are required to examine whether moderate net ultrafiltration rates compared with slower and faster rates are associated with reduced risk of hemodynamic instability, organ injury, and improved outcomes.