This review provides a perspective on the role of IL-4 in relation to both normal and leukemic CLL B cells. IL-4 is a well-characterized cytokine known to be produced by normal T cells and have impact on normal B cell differentiation and proliferation. This cytokine and its receptor are now known to exist on CLL B cells. An autocrine pathway for CLL B cells is strongly supported by signaling events, alteration of apoptotic proteins and changes in apoptosis resistance. Based on the increasing knowledge regarding the IL-4 pathway unique opportunities for therapy are now available in B-CLL.