The immune system possesses significant cytotoxic potential. Stimulating natural immunity through vaccination has shown promising effects in some cancers; however, a number of barriers limit the efficacy of the natural immune system including tolerance to self-antigens and immunodeficiency associated with cancer and associated chemotherapy. Adoptive immunotherapy using T-cells that are genetically modified to express an artificial receptor that combines the antigen specificity of an antibody with the signal transduction machinery of the T-cell receptor in a single chimeric antigen receptor (CAR) hold significant promise for overcoming many of the barriers to anti-cancer immunity. This talk will describe the clinical applications of CARs that target CD19, a molecule expressed by normal B-cells and cells in a range of B-cell malignancies including acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) as well as a CARs targeting BCMA for multiple myeloma and mesothelin for solid malignancies. Toxicity related to this cell therapy that includes a cytokine release syndrome and long term B-cell aplasia will also be discussed.