The primary focus of this review is to 1) review the literature on the regulation and outcome of the mTOR signaling pathways from a basic research perspective, and 2) summarize the use of mTOR inhibitors to target aberrant mTOR activation and signaling in hematological diseases, such as acute leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, GVHD, and Waldenström macroglobulinemia. This evidence concerns the gene MTOR and Waldenstrom macroglobulinemia.