CD40, CD40L, and sCD40, as important signaling molecules, play a great role in inducing antigen-presenting cells, T cell activation, and tumor immunology. This paper investigates these three signaling molecules in pathogenesis of acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphoblastic leukemia, lymphoma, and multiple myeloma, and clinical significance of using immunologic CD40 bound drugs, such as CD40L trimer, CD40 monoantibody, and CD40L positive cell, in treating hematologic malignancies.