Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults and usually affects the elderly patient. More than 50% of CLL cases are diagnosed at an early disease stage, often as an incidental lymphocytosis found in a routine blood screen. For about 40 years, the classifications according to Binet or Rai have been the hands-on staging systems to stratify patients in daily clinical practice. An increasing molecular understanding of the disease and the identification of strong prognostic markers, such as genetic lesions in TP53, have urged clinical scientists to create new scoring systems that improve prognostic risk assessment and treatment allocation. Until today, studies on early treatment interventions in asymptomatic patients using single chemo- or combined chemoimmunotherapy have failed to demonstrate a survival benefit. However, improved risk stratification tools integrating molecular disease features and the availability of new targeted drugs with attractive efficacy and limited toxicity might open new possibilities to re-investigate early treatment in well-defined clinical settings in the future.