Enhanced postoperative recovery programmes (ERAS) were developed about 20 years ago based on improved understanding of the pathophysiology of postoperative recovery within an integrated multidisciplinary approach. The results across surgical procedures have been extremely positive with a reduction in hospitalisation and medical complications, without increased re-admission rates. However, several challenges lie ahead including improved implementation of existing scientific evidence, increased focus on post-discharge recovery problems and a need for improved design of future ERAS studies. However, the most important challenges lie within a better understanding and control of undesirable peri-operative pathophysiological responses with subsequent risk of organ dysfunction. These efforts should focus on: the inflammatory and neurohumoral surgical stress responses; fluid management; pain management; blood management; mechanisms of orthostatic intolerance; postoperative cognitive dysfunction; risk factors for thrombo-embolic complications; and mechanisms and prevention of postoperative ileus. Finally, more focus should be made on the different barriers to post-discharge functional recovery and the choice of (pre- and postoperative) rehabilitation. These efforts should be made on a procedure-specific as well as on a patient-specific basis.