In this brief overview, recent progress and current status of blood substitute research and development is summarized. Current blood substitute development efforts are focused on red blood cell substitutes but substitutes for platelets and other blood components are also in progress. Red cell substitutes currently in various stages of development are semi-synthetic or synthetic oxygen carriers that include "stealth" or "masked" red cells, hemoglobin-based oxygen carriers and perfluorocarbon-based oxygen carriers. Artificial platelets (or platelet substitutes) are in early stages of development and include human platelet fragments or particles of synthetic/semi-synthetic materials or recombinant human serum albumin coupled with platelet surface receptor fragments. Of note, some recombinant clotting factors (Factors VII, VIII, IX) have already been successfully developed and licensed for treatment of hemophilia. In addition, some future approaches and prospects of blood component replacement therapeutics are discussed.