Reliable hemocompatibility testing of a biomaterial has to be done in consideration of the intended application in the final medical product. The testing conditions should reflect the fact that hemocompatibility is less an independent and immanent characteristic of a material itself but has to be viewed as the interaction of a material with the surrounding environment.Considerations on the use of whole human blood versus blood fractions are discussed. A reliable incubation of whole blood has to be in accord with several prerequisites including a careful selection of donors, care during blood drawing, and appropriate anticoagulation. Several anticoagulants and their application for various tests are considered. Blood incubation can be performed in stagnant, agitated, or flowing conditions-each having specific advantages depending on the experimental objective. Concerning the incubation system, a practical design is favored, enabling fast blood processing, a big contact area between blood and the test material, while avoiding the contact of blood with air. The most commonly used incubation settings, i.e., parallel plate chambers and the Chandler loop are introduced.In the third section, markers for thrombogenicity and inflammation are presented. Due to the complexity of blood reactions there is no single parameter that enables an easy and fast estimation of thrombogenicity. Global parameters like thrombus formation assays permit just a rough estimation of surface- induced thrombogenicity. A more detailed explanation of material-induced blood activation processes can be gained using several humoral and cellular markers for coagulation and immunologic reactions. An overview of the significance and limitations of robust parameters for thrombin formation (TAT, F1. +. 2), complement (C5a, C3a, sC5b-9), platelet (PF4, CD62p), and granulocyte activation (PMN elastase, CD11b) among others is provided.