Monoclonal antibody (moAb)-based therapies are evolving as an integrated component in the treatment of chronic lymphocytic leukemia (CLL). Advantages such as different mechanisms of action (compared with those of chemotherapy), no or minimal stem cell toxicity, as well as the absence of hair loss and delayed nausea may result in a rapidly increasing usage of these agents in different phases of the disease. The combination of moAbs with chemotheraputic agents has shown promising results in early studies as well as their role in the eradication of minimal residual disease (MRD). The availability of an increasing number of new moAbs together with a better understanding of their effector function will hopefully lead to improved therapeutic outcomes for patients with CLL and related disorders.