B-cell chronic lymphocytic leukemia increasingly is being recognized as a useful model disease with which to study more general processes involved in the evolution of neoplastic disease. The accessibility of the tumor cells and the capacity to confirm their clonal relatedness allow for evaluation of the processes associated with neoplastic transformation and/or disease progression. Recent studies have provided fascinating insight into the potential pathogenesis and pathophysiology of this disease. In addition, features of leukemia cells have been identified that can distinguish subsets of patients that have different tendencies for disease progression. Gene expression studies have identified a relatively small number of genes that are differentially expressed between these subsets, allowing for focused attention on proteins that might contribute to the noted differences in clinical behavior. Finally, recognition that chronic lymphocytic leukemia cells depend upon specific microenvironmental growth and survival factors identifies novel targets for disease intervention. This article focuses on the reports of the past year that have contributed to these areas of active research on chronic lymphocytic leukemia, the most common adult leukemia in Western societies.