Monoclonal B-cell lymphocytosis (MBL) is a clonal B-cell disorder characterized by less than 5 × 109/L B lymphocytes in the peripheral blood, with a characteristic immunophenotype and no lymphadenopathy or organomegaly. The vast majority of MBL cases express the immunophenotype of chronic lymphocytic leukemia (CLL; CLL-like MBL), although non-CLL MBL also exists. CLL-like MBL, which is the focus of this review, is divided into low-count MBL (median B-cell count: 0.001 × 109/L, typically identified in population-based screening studies using highly sensitive flow cytometry assays) and high-count MBL (clinical MBL, median B-cell count: 2.9 × 109/L, typically identified during the workup of low-level lymphocytosis). Low-count MBL has an exceedingly small risk of progression to CLL, and these patients do not require any specific follow-up. In contrast, patients with high-count MBL have a 1% to 2% per year risk of progression to CLL requiring therapy, as well as a higher risk of infectious complications and secondary malignancies. Although the overall survival of high-count MBL patients collectively is similar to the age- and sex-matched general population, 5-year survival for high-count MBL with higher-risk biologic parameters appears to be slightly lower than that of the general population. This review summarizes key concepts in the classification, diagnosis, and biology of CLL-like MBL and addresses several important issues in clinical management.