Given the crucial role played by Notch signaling and Bcl-2 expression in T-ALL development and progression, as well as the pressing need for novel treatments in relapsed/refractory (R/R) cases, we will explore, in the present review, the role of single treatments in the context of T-ALL and the current knowledge about their combined effect, giving some insights into how these inhibitors could help to improve responses to conventional therapy. The gene discussed is BCL2; the disease is acute lymphoblastic leukemia.