Nanoparticles and nanostructured materials are increasingly used in medical applications. Understanding a nanoparticle’s interactions with the biological system is extremely important, given that nanoparticles may exhibit unique and potentially hazardous properties due to their small size, shape, composition, and route of administration. Evaluating the hemocompatibility of nanoparticles in human blood can be critical in the design of nanoparticles for in vivo application. Many nanoparticle products are designed for intravenous administration, for example in targeted drug delivery, as contrast agents for imaging or as vaccine carriers. It is thus of great importance to evaluate their potential to trigger inflammatory responses and to perform a complete risk assessment on their adverse effects on human blood. Clotting, complement activation, thrombocyte (platelet) activation, leukocyte activation, and hemolysis are all processes that warrant special attention.