This chapter discusses various aspects of rejection. It is defined as a recipient’s immune response to foreign antigens expressed by the donor that if unresolved will lead to graft loss. Rejection’s classification is based on pathology and concurrent antibody data – Banff classification. The different types of acute rejections are hyperacute, cellular and antibody mediated rejection. Hyperacute rejection is rare event due to antibodies targeting HLA, blood group, and/or other endothelial antigens leading to rapid complement activated thrombotic microangiopathy with extensive hemorrhage and infarction. Antibody mediated rejection (injury) requires the presence of antibody and indirect evidence of active endothelial injury by demonstration of complement activation. Rejection monitoring currently is reactive rather than proactive. Evaluation is initiated based on changing kidney function determined by a rise of serum creatinine. More sensitive noninvasive biomarkers of rejection include blood and urinary screens for inflammatory cytokines and enzymes associated with T and B cell activation.