OBJECTIVES: Assess the annual number of patients with chronic lymphocytic leukemia (CLL)/small cell lymphocytic leukemia (SLL) who relapse or are refractory to first line therapy in selected European countries. METHODS: A systematic literature review, aiming to identify and summarize all evidence related to outcomes of current treatment options for CLL/SLL was conducted. A comprehensive literature search of two databases (PUBMED and Cochrane) from 2005-2014, and proceedings from major hematology/oncology conferences was undertaken. In addition, data from various cancer registries, surveillance and cohort studies were analyzed. Incidence and prevalence of CLL/SLL was calculated and patient outcomes (e.g. overall response rate [ORR] and progression-free survival [PFS]) were summarized. Data analysis was stratified for subpopulations by age, ECOG performance status, presence of del17p and first-line treatment options available in the countries under study (Belgium, France, Germany, Italy, Netherlands, Poland, Spain, Sweden and the UK). RESULTS: The incidence of CLL/SLL ranges from 4.9 to 6.9 per 100,000 in the countries under study. The estimated number of newly diagnosed patients each year with CLL/SLL in Europe ranges from 19,383 to 26,411. ORR after first line chemo-immunotherapy ranged from 63% to 95%, with complete response rates ranging from 5% to 47%. PFS rates ranged from 19 to 80 months. Based on evidence derived from this review, the steady-state prevalence of patients with relapsed or refractory CLL/SLL resulted in 9,174 to 19,579 patients annually, requiring second line treatment in the countries under study. CONCLUSIONS: CLL/SLL represents the largest adult leukemia in the western world. This systematic literature review identified the significant number of patients failing first-line therapy with relapsed or refractory disease. Despite the improved response rates achieved in the last decade, duration of response varies, with some patients having short durations only. Therefore, further improvement in treatment options is required.