The therapeutic target of extracorporeal carbon dioxide removal (ECCO₂R) is the elimination of carbon dioxide (CO₂) from the blood across a gas exchange membrane without influencing oxygenation to a clinically relevant extent. In acute respiratory distress syndrome (ARDS), ECCO₂R has been used to reduce tidal volume, plateau pressure, and driving pressure (“ultraprotective ventilation”). Despite achieving these goals, no benefits in outcome could be shown. Thus, in ARDS, the use of ECCO₂R to achieve ultraprotective ventilation can no longer be recommended. Furthermore, ECCO₂R has also been used to avoid intubation or facilitate weaning in obstructive lung failure as well as to avoid mechanical ventilation in patients during bridging to lung transplantation. Although these goals can be achieved in many patients, the effects on outcome still remain unclear due to lack of evidence. Despite involving less blood flow, smaller cannulas, and smaller gas exchange membranes compared with extracorporeal membrane oxygenation, ECCO₂R bears a comparable risk of complications, especially bleeding. Trials to define indications and analyze the risk–benefit balance are needed prior to implementation of ECCO₂R as a standard therapy. Consequently, until then, ECCO₂R should be used in clinical studies and experienced centers only. This article is freely available.