Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in Europe and it remains incurable. Targeted therapies have revolutionized the treatment of CLL. However, many patients develop resistance, have severe side effects or relapse during treatment. There is an unmet medical need for tailoring optimal therapy for each patient in order to prevent ineffective treatment and toxic side effects. The CLL-CLUE project will identify multi-omics biomarker panels and implement artificial intelligence-based clinical decision support systems to guide personalised treatment decisions. We expect that this will lead to significantly increased treatment efficacy, individualization of therapy and reduced drug use and side effects. In addition, reduced consumption of drugs and cost-effective outcomes will lower financial stress that the health care providers and patients experience.