Chronic lymphocytic leukemia (CLL) is a clonal malignancy of mature B cells that displays immense clinical heterogeneity as reflected by the observation that many patients have an indolent disease that will not require intervention for many years while others will present with an aggressive and symptomatic leukemia requiring immediate treatment. Although there is no cure for CLL, the disease is treatable and current standard chemotherapy regimens have been shown to prolong survival. There is no obvious survival advantage to early treatment versus observation but the timing as to when a patient will require treatment is highly unpredictable. Thus, there has been great interest in identifying prognostic markers that can be used to distinguish those patients who may have an aggressive form of CLL and might benefit from early intervention. While clinical staging systems have been used to stratify patients into risk categories, they lack the ability to predict disease progression or response to therapy. Recent advances in our understanding of the biology of CLL have led to the identification of numerous cellular and molecular markers with potential prognostic and therapeutic significance. This review provides a concise overview of prognostic markers in CLL and a discussion of how those markers have impacted the clinical management of the disease.