Dialysis as renal replacement therapy aims excess water and waste solutes from the uremic patient while retaining proteins in the plasma. Irrespective of the dialysis modality, hemodialysis (HD) or peritoneal dialysis (PD), the amount and composition of proteins that are removed are important determinants of the biocompatibility of the therapy. Although hemodialysis membranes would ideally be biologically inert filtration tubes, they are known to adsorb proteins. The part of the plasma proteome that is thereby removed during every dialysis session may be regarded as the extracorporeal proteome, which has to be kept in balance with the plasma proteome, regarding the individual proteins biological roles and activation states. In a recent study, Ronci et al. (Proteomics Clin. Appl. 2018, e1700140) comprehensively compare two hemodialyzer membrane materials by shotgun LCMS proteomic analysis of adsorbed proteins and ultrafiltrates from four HD patients. While pathway analysis is an attractive tool to compare different proteomes on an abstract level, some challenges remain regarding the adaptation for such tools for special proteomes and the interpretation of relative changes compared absolute changes regarding their biological importance in dialysis techniques. In summary, selective protein removal may represent a yet unexploited therapeutic opportunity if the “right” proteins are removed from the blood.