Chronic lymphocytic leukemia (CLL) remains the most prevalent form of leukemia in the Western world, with no cure to date. Ongoing and essential research into this heterogeneous disease has led to a number of new treatment options becoming available to CLL patients in the past decade. The present review presents the recent developments in the field of CLL treatment, with the main focus on elderly patients and CLL patients with coexisting comorbidities. The review discusses the current treatment regimens that provide the most promising outcomes for patients in this subgroup, with a number of important clinical trials summarized. These clinical trials, which have investigated promising single-agent therapies or combination therapies, are discussed, with an emphasis on the efficacy and tolerability for patients aged ≥ 65 years. Also, the misrepresentation of the true CLL population in many clinical trials and the need for better guidelines for participant inclusion criteria to provide a more realistic and accurate study population are noted.