New knowledge about the biology of B-CLL can provide clues for novel therapeutic targets. For example, since B-CLL cells must interact with the stroma in bone marrow or other peripheral lymphoid tissues to survive, furthering our knowledge of these interactions may generate new objectives for innovative therapies. Another compelling set of options may derive from specific inhibition of the BCR or CD38 signalling pathways or other pathways in which ZAP-70 is crucial. Likewise, the possibility of using cell-cycle-specific drugs is worth being explored in clinical trials, given the documented active turnover of B-CLL cells. Finally, because up to 20% of patients with the worst prognostic markers have stereotypic antigen receptors, these common structures may be feasible as vulnerable points of attack. As the antigens that engage these receptors become more precisely defined, it may be possible to use these to develop an arsenal of specific therapies.