Bioengineers have contributed to biocompatibility research. Many materials have been designed, synthesized and characterized by use of various analytical instruments. The blood compatibility of materials has been studied by focusing on the blood–material interfacial reactions. Although much information has been accumulated regarding such local reactions, understanding of biocompatibility is still limited. A more global approach to study is needed. A new approach to understanding biocompatibility is proposed and discussed. Three points are stressed: interaction within body's defense system and its effect on blood–material reactions; induction of a systemic reaction by a local reaction, which then affects the blood–material interaction; the time sequence of such interactions between local and systemic reactions. To establish a logical approach to study biocompatibility is most important at this moment for the future progress in biocompatibility research.