Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults, and it has been shown to cause considerable symptom burden in both patients and their caregivers. Recently, studies have focused on quality-of-life (QOL) measures and the relationship with health outcomes. However, to date, the breadth of QOL domains and measures is not well represented in the literature, diminishing the ability to form specific questions and to develop a systematic review. Objective: The objective of this scoping review was to investigate and analyze articles related to CLL patient and caregiver physical, psychological, social, and spiritual well-being published between January 1, 2015, and June 15, 2020. These articles will be used to provide an evidence base for the development of an integrative education tool to empower patients and their caregivers following a CLL diagnosis and throughout the continuum of care. Methods: This scoping review considered all studies that addressed physical, psychological, social, and spiritual well-being of patients diagnosed with CLL or their caregivers. A 3-step search strategy was undertaken: (1) an initial limited search of PubMed; (2) an extensive search using all identified keywords and index terms; and (3) a hand search of the reference lists of included articles. This review was limited to studies published in English between January 1, 2015, and June 15, 2020. Reviewers extracted data independently; disagreements that arose between the reviewers were resolved via discussion or with a third reviewer. Results: A total of 5629 articles were screened, 937 full-text publications were reviewed, and 75 relevant articles were identified. Most studies focused on physical well-being. Several review articles discussed treatment algorithms and consideration for treatment of patients with CLL. No articles evaluating the patient/ caregiver relationship were identified, and only a single study was designed to assess caregiver health status. Conclusion: The most commonly evaluated QOL component was physical well-being, whereas only a single article discussed spiritual well-being. Social well-being was discussed in 4 articles. Overall, 8 articles spanned the psychological and physical domains. Inclusion of all 4 QOL components will be beneficial for developing a patient education platform for patients and their caregivers following a diagnosis of CLL and throughout the care continuum.