Multiorgan failure is among the most frequent reasons of death in critically ill patients. Based on extensive and long-term use of renal replacement therapy, extracorporeal organ support became available for other organ failures. Initially, most of these techniques (e.g. extracorporeal membrane oxygenation, extracorporeal CO2 removal [ECCO2R] and extracorporeal liver support) were used as stand-alone single organ support systems. Considering multiple interactions between native organs (“crosstalk”), combined or integrated extracorporeal organ support (ECOS) devices are intriguing. The concept of multiple organ support therapy (MOST) providing simultaneous and combined support for different failing organs was described more than 15 years ago by Ronco and Bellomo. This concept also implicates overcoming the “compartmentalized” approach provided by different single organ specialized professionals by a multidisciplinary and multiprofessional strategy. The idea of MOST is supported by the failure of several recent studies on single organ support including liver and lung support. Improvement of outcome by ECOS necessarily depends on optimized patient selection, integrated organ support and limitation of its side effects. This implicates challenges for engineers, industry and healthcare professionals. From a technical viewpoint, modular combination of pre-existing technologies such as renal replacement, albumin-dialysis, ECCO2R and potentially cytokine elimination can be considered as a first step. While this allows for stepwise and individual combination of standard organ support facilities, it carries the disadvantage of large extracorporeal blood volume and surfaces as well as additive costs. The more intriguing next step is an integrated platform providing the capacity of multiple organ support within one device. (This article is freely available.)