Upon contact with bodily fluids/tissues, exogenous materials spontaneously develop a layer of proteins on their surface. In the case of biomedical implants and equipment, biological processes with deleterious effects may ensue. For biosensing platforms, it is synonymous with an overwhelming background signal that prevents the detection/quantification of target analytes present in considerably lower concentrations. To address this ubiquitous problem, tremendous efforts have been dedicated over the years to engineer protein-resistant coatings. There is now extensive literature available on stealth organic adlayers able to minimize fouling down to a few ng cm⁻², however from technologically irrelevant single-protein buffered solutions. Unfortunately, few coatings have been reported to present such level of performance when exposed to highly complex proteinaceous, real-world media such as blood serum and plasma, even diluted. Herein, we concisely review the surface chemistry developed to date to minimize fouling from these considerably more challenging blood-based fluids. Adsorption dynamics is also discussed.