A dramatic change has taken place in therapy for chronic lymphocytic leukemia over the past 15 years. In 1990, available therapy produced complete responses in less than 5% of treated patients. This is in marked contrast to modern regimens, which can reliably produce complete responses in over 50% of patients. This remarkable improvement is completely attributable to the introduction of new active agents. These new agents include three purine analogues (pentostatin, fludarabine, and cladribine) and two monoclonal antibodies (rituximab and alemtuzumab). Novel combinations of these agents have emerged as effective new therapies for previously untreated and pretreated patients. Clinical studies indicate that such combinations can induce higher response rates--including complete responses--than single-agent therapy. Those patients who achieve a complete response have superior survival, compared with those who only achieve a partial response. Though not yet demonstrated in a prospective randomized trial, treatment approaches aimed at achieving high-quality responses may one day lead to an improvement in survival for patients with chronic lymphocytic leukemia and, ultimately, offer the hope of curative therapy in these patients.