Background: Economic evaluations are widely used to predict the economic impact of new treatment alternatives. Comprehensive economic reviews in the field of chronic lymphocytic leukemia (CLL) are warranted to supplement the existing analyses focused on specific therapeutic areas. Methods: A systematic literature review was conducted based on literature searches in Medline and EMBASE to summarize the published health economics models related to all types of CLL therapies. Narrative synthesis of relevant studies was performed focusing on compared treatments, patient populations, modelling approaches and key findings. Results: We included 29 studies, the majority of which were published between 2016 and 2018, when data from large clinical trials in CLL became available. Treatment regimens were compared in 25 cases, while the remaining four studies considered treatment strategies with more complex patient pathways. Based on the review results, Markov modelling with a simple structure of three health states (progression-free, progressed, death) can be considered as the traditional basis to simulate cost effectiveness. However, more recent studies added further complexity, including additional health states for different therapies (e.g. best supportive care or stem cell transplantation), for progression-free state (e.g. by differentiating between with or without treatment), or for response status (i.e. partial response and complete response). Conclusions: As personalized medicine is increasingly gaining recognition, we expect that future economic evaluations will also incorporate new solutions, which are necessary to capture a larger number of genetic and molecular markers and more complex patient pathways with individual patient-level allocation of treatment options and thus economic assessments.