Infections are a primary cause of death in patients with chronic lymphocytic leukemia (CLL). Such individuals are particularly susceptible to infectious complications stemming from immune deficits associated with the primary disease process and with immunosuppression secondary to treatment. Although the recent availability of new treatment modalities and more aggressive therapies are improving outcomes for patients with CLL, standardized approaches are needed so that nurses can monitor for and manage infections. The aim is overall reduction in morbidity and mortality, as well as improvement in quality of life. The current pharmacologic therapies for CLL are alkylating agents, purine nucleoside analogs, monoclonal antibodies, and combinations of those therapies, which may present their own unique risks for and different spectra of infectious events. This article provides an overview of the known risks for developing infections in CLL, as well as nursing guidelines for monitoring and managing patients with CLL.