Over the last few years, renewed interest in clinical trials for patients with chronic lymphocytic leukemia has been stimulated by both an increase in our understanding of the biology and immunology of the disorder, as well as the development of several new, unique, and effective chemotherapeutic agents. The most interesting of these compounds are the purine nucleosides: Fludarabine phosphate, 2'-deoxycoformycin (DCF), and 2-chlorodeoxyadenosine (CDA). Phase I and II clinical trials are under way in previously treated patients with advanced CLL evaluating fludarabine and DCF in combination with each other or with chlorambucil. A national Phase III trial is comparing several of the more promising of these combinations with standard therapy (e.g., chlorambucil) in previously untreated patients. We also have new data for developing a more precise staging system.