The Defense Advanced Research Projects Agency (DARPA) is soliciting innovative proposals in support of the Smart Red Blood Cells program (Smart-RBC). The DARPA Smart-RBC program aims to engineer red blood cells to contain novel biological features that can safely, temporarily, and reliably alter human physiology. Specifically, the Smart-RBC program will revolutionize blood products by creating “smart red blood cells” (SRBCs). SRBCs will be engineered to contain additional biological circuits consisting of three layers: Sense extracellular biomarkers; Decide next steps; Act by creating effector molecules that can alter metabolism or physiology. The program will identify the art-of-the-possible to create SRBCs to enhance human performance and maximize survival via hemostasis products. This program does not include clinical trials or direct human testing.