Background: The clinical development landscape for chronic lymphocytic leukemia (CLL) is evolving rapidly, and continuously challenges current therapeutic guidelines. Several new agents have recently gained approval from the US Food and Drug Administration and European Medicines Agency, including venetoclax, ibrutinib, idelalisib, and obinutuzumab. These new therapies, together with recent updates to the guidelines from the National Comprehensive Cancer Network and European Society for Medical Oncology, reflect findings of improved progression-free and overall survival rates, and represent a new age in the treatment of CLL. This is the last part of a 3-part series. Objective: The objective of this 3-part article is to provide an overview of recent changes to the CLL landscape, as well as future directions to inform providers and clinical researchers. Discussion: Because of these changes, it is likely that the future will bring further development of niche drugs that target cytogenetic abnormalities, specifically 11q and 17p deletion, as well as more active and tolerable regimens for older patients. Tolerable regimens and convenient routes of administration are needed to enable outpatients to self-administer their treatment long-term, and improve their quality of life. Conclusion: The increasing number of novel agents for CLL management presents new challenges for appropriate sequencing of these medications, and comparator arm choices for future clinical trials. Collaboration between drug developers can lead to more efficient and less costly clinical trials. Increased enrollment in clinical trials, especially among older patients, will be critical for the continued development of novel agents for the treatment of CLL. [ABSTRACT FROM AUTHOR]