In addition to the extensive work that has been conducted in order to understand better the biological features of the leukemic population in B-cell chronic lymphocytic leukemia (CLL), over the years considerable interest has been directed towards other related studies that may have important implications for the accumulation of the leukemic clone and for the immunoparesis typical of this disease. In the present review article, we discuss some of these areas of investigation and, in particular, we focus on: (1) the multiple abnormalities recorded within the T and cytotoxic compartment of patients with CLL; (2) cytokine loops occurring in this disease, with particular emphasis on the cytokines that appear to play a more critical role; and (3) the cell-to-cell cross talk that may be actively operational in CLL. These findings will be discussed in relation with the possible implications that each of them have in the expansion and clinical behavior of a disease that is increasingly proving its heterogeneity.