Hematologic cancers, including lymphomas (Hodgkin and non-Hodgkin), leukemias (acute lymphoid, acute myeloid, and chronic lymphocytic), and plasma cell cancers (multiple myeloma and WaldEnstrom’s macroglobulinemia) hold a special place in the history of cancer immunotherapy development. Hematologic malignancies, as cancers of immune cells themselves, represent a unique setting and challenge to immunotherapy: we must turn the immune system “on itself” to fight malignant forms of leukocytes. In this lies the challenge to exploit antigenic, genetic, and phenotypic differences between normal and transformed cells, most often pitting effector and target cells of the same lymphoid lineage against each other.