Chronic lymphocytic leukemia (CLL) is a slow lymphoproliferative disease. The therapy has only a palliative effect and therefore the common attitude to the therapy is conservative (watch and wait policy). Monotherapy with alkylating cytostatics, usually chlorambucil, is considered by most authors to be the therapy of first choice. Only the French study showed superiority of polychemotherapy CHOP over monotherapy. New drugs for the treatment of chronic lymphocytic leukemia are purine-analogs. Fludarabine has been used mostly of this purine-analogs. The response rate to fludarabine therapy is 30-45% in pretreated patients and the response rate in the chemotherapy-naive patients is about 80%. 2-chlorodeoxyadenosine was used in the same indications and it showed that this drug had a similar effect in this disease as fludarabine. The contemporary indication for fludarabine is standard-chemotherapy-refractory disease. Whether this drug will be used for initial therapy, is a question. Interferon alpha is therapeutically active in early stages of chronic lymphocytic leukemia, but it is unclear, if this response has any influence on survival. Interferon alpha is ineffective in advanced stages of this disease. The role of interferon alpha as the maintenance treatment after chemotherapy is heavily discussed.