Background. Chronic lymphocytic leukemia (CLL) is the mo st common form of adult leukemia in the western European countries and is characterized by the relentless accumulation of monoclonal B cells with the appearance of small mature lymphocytes and with a characteristic immunophenotype. Even with the right trea tment, this disease is known to have a variable course: some patients die within one year after diagnosis while others live for longer than ten years. Case report. A 59 year old female with a past medical history of ischemic cardiopathy and hypothyroidism was admitted to the Haematology Unit of Mures County Emergency Hospital with severe anemia, chronic fatigue and leukocytosis. After the anemia was corrected, the diagnosis of chronic lymphocytic leukemia was confirmed by complete blood count and immunophe notyping for which the patients was only observed for 2 years. Due to the secondary severe anemia the treatment with Fludarabine is started as monochemotherapy first line treatment. After one month the patient is hospitalized with severe anemia with Coombs ’ test positive for which methylprednisolone is administered for one week and COP chemotherapy is induced. Because of the gastrointestinal side effects, the COP chemotherapy is ceased and Fludarabine treatment is reintroduced. The treatment is continued fo r one year but the multiple side effects (hemolytic anemia, herpes zoster, Listeria meningitis) determined cessation of Fludarabine and Chlorambucil treatment was introduced. The treatment with Chlorambucil was continued for 3 years. Even though the patien t supported well the treatment, the splenomegaly has progressively increased (from 3 cm to 8 cm) and the infectious diseases appeared (Acinetobacter pneumonia and pharyngeal candidiasis). Conclusions. Even though the treatment is accordingly to the actual international guides, the individual responsibility to the drugs and the unpredictable evolution of this disease may be a challenge in treating chronic lymphocytic leukemia.