Chronic lymphocytic leukemia (CLL) is a malignancy mainly affecting elderly people and is still considered an incurable disease. Despite recent advances in CLL treatment, relapse rates are high and often accompanied by the development of resistance towards conventional chemotherapy. Thus, new agents are needed for the treatment of these patients. In recent years, our understanding of the biological mechanisms driving CLL pathogenesis has considerably improved, and novel treatment strategies are arising. This review summarizes recent insights in CLL biology and describes several new agents and treatment strategies that are currently explored in pre-clinical studies and early-phase clinical trials.