Chronic lymphocytic leukemia (CLL) is the most common adult leukemia for which therapeutic options remain unsatisfying as cure has remained elusive. Recent laboratory discoveries and promising results from completed phase III studies with fludarabine provide reason to reassess therapeutic goals in the treatment of patients with symptomatic CLL. Early enrollment of patients on protocols using combination therapies with fludarabine and new agents such as flavopiridol, IDEC-C2B8, Campath-1H, UCN-01, bryostatin, FR 901228, and melarsoprol will hopefully represent the next advance to improved overall survival and ultimately the cure of CLL.