Over the last decade, there is a surge on researchers utilizing Surface Enhanced Raman Scattering (SERS) spectroscopy for blood analysis for various biomedical applications. This chapter starts with a brief review of SERS substrates and Raman instrumentation for SERS detection. Then four types of SERS based blood analysis methodologies are discussed with application examples including (1) label-free SERS methods for detection of intrinsic ingredients and exogenous substances in blood, sera, and plasma; (2) detection of circulating tumor cells in blood by SERS tags for cancer diagnosis; (3) labeling-free SERS analyses of human serum and plasma for disease diagnoses; and (4) combining membrane electrophoresis for serum protein separation with SERS analysis for cancer detection. At the end, we present a new technology based on electroporation for nanoparticle delivery into blood cells for intracellular SERS analysis.