Intravascular gas exchange, in which miniaturized hollow fibre oxygenators are inserted into the caval veins, has been proposed as a simpler and safer alternative to extracorporeal support in severe respiratory failure. One such device, the IVOX (intravascular oxygenator), has undergone clinical trials (160 implants) and, despite individual benefits, was found to be limited in its gas exchanging capacity. The peculiarities of oxygen physiology render pre-pulmonary oxygenation inefficient and variable, whereas carbon dioxide clearance is much more predictable. Several devices are currently undergoing development and may offer substantially enhanced gas exchange. The new devices, which may be several years from widespread clinical assessment, offer exciting therapeutic options in severe respiratory failure but are unlikely to completely replace extracorporeal techniques in the most severe forms of respiratory failure.