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CD47 is a 50 kD transmembrane protein receptor to the Ig superfamily that can manifest in four isoforms, differing only in the length of their cytoplasmic tail. CD47 is involved in various cellular processes including apoptosis, proliferation, adhesion, and migration, and plays a key role in immune and angiogenic responses. CD47 was first identified as a tumor antigen on human ovarian cancer and its expression has subsequently been found on multiple human tumor types such as acute myeloid leukemia (AML), chronic myeloid leukemia, acute lymphoblastic leukemia (ALL), non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM), bladder cancer, and pediatric and adult brain tumors. CD47 interacts with membrane integrins, TSP-1, and SIRPα. The CD47/SIRPα interaction results in the inhibition of phagocytosis by macrophages thus, allowing cancer cells to multiply unchecked. Anti-CD47 antibody is a potential therapeutic target in a variety of cancers and for the treatment of pulmonary fibrosis. Anti-CD47 antibody treatment not only facilitates macrophage phagocytosis of cancer, but also promotes the activation of cancer-specific lymphocytes by acting as a beacon, flagging cancer cells which now display altered proteins to which the immune system can react.