Higher organisms defend themselves against invading micro-organisms and harmful substances with their immune system. Key players of the immune system are the white blood cells (WBC), which in case of infection move in an extravasation process from blood vessels toward infected tissue promoting inflammation. This process starts with the attachment of the WBC to the blood vessel wall, mediated by protein pair interactions of selectins and counter-receptors (C-R). Individual selectin C-R binding is weak and varies only moderately between the three selectin types. Multivalency enhances such small differences, rendering selectin-binding type specific. In this work, we study selectin C-R binding, the initial step of extravasation. We performed electrostatic energy computations based on the crystal structure of one selectin type co-crystallized with the ligating part of the C-R. The agreement with measured free energies of binding is satisfactory. Additionally, we modeled selectin mutant structures in order to explain differences in binding of the different selectin types. To verify our modeling procedures, surface plasmon resonance data were measured for several mutants and compared with computed binding affinities. Binding affinities computed with soaked rather than co-crystallized selectin C-R structures do not agree with measured data. Hence, these structures are inappropriate to describe the binding mode. The analysis of selectin/C-R binding unravels the role played by individual molecular components in the binding event. This opens new avenues to prevent immune system malfunction, designing drugs that can control inflammatory processes by moderating selectin C-R binding.