Non-Hodgkin’s Lymphoma (NHL) is responsible for 4% of all cancer cases in the United States, but its conventional treatment options have experienced limited success. Patients develop resistances to the standard chemotherapy, CHOP, as well as Rituximab, a chemosensitizing agent used in concert with CHOP. Chimeric antigen receptor T cell (CAR-T cell) therapy may be a viable option for patients with refractory/relapsed NHL. In this new immunotherapy, a CAR is genetically added to the surface of T cells, allowing the patient’s own T cells to selectively recognize, bind and eliminate malignant B cells. CARs are typically engineered to be CD19 specific as that is a common antigen on B cells, allowing the recognition of malignant B cells such as those present in NHL. However, there have been cases that show the development of resistances to CD19 CAR-T cells, as well as fatal cases of cytokine storm that result from cytokine release by active CAR-T cells after completion of the treatment. To address these problems and improve the efficacy of CAR-T cell immunotherapy, CAR therapy could be used in combination with FDA-approved drugs such as histone deacetylase inhibitors (HDACis) or celecoxib (Celebrex), or it could incorporate a suicide gene. The suicide gene may be implemented with gene-directed enzyme prodrug therapy (GDEP), CRISPR/iCasp9, or therapeutic mAb-mediated mechanisms.