Infectious complications continue to be one of the major causes of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). The pathogenesis of infections in these patients is multifactorial (Wadhwa & Morrison, 2006). Predisposition to infection in CLL is mediated through various abnormalities including both the immune defects inherent in the primary disease (impairment in humoral and cellular immunity) and in the further immunosuppression related to management of CLL (Morra et al., 1999). Increased infectious events may arise from the multiple courses of immunosuppressive therapy and progressive deterioration of a patient's immune system over the course of disease (Elter et al., 2009). Hypogammaglobulinemia is an important predisposing factor for infection in patients with early-stage disease and for those treated with conventional alkylating agents (Wadhwa & Morrison, 2006). It is probably the most important immune defect increases the risk of severe bacterial infections and its frequency and severity has direct relationship with the duration of the disease (Morra, et al., 1999). The majority of disease-specific complications in CLL, notably infection and autoimmunity, relate to the underlying alterations in immune function. Both cellular and humoral immunity are impaired with qualitative and quantitative defects in B cells, T cells, NK cells, neutrophils and the monocyte/macrophage lineage. Virtually all patients have reduced immunoglobulin levels, even in early stages, and this is associated with an increased frequency and severity of infection (Dearden, 2008). The immunodeficiency chiefly manifests as hypogammaglobulinaemia but involves all elements of the immune system. It is caused by the interpolation of tumor cells among immunological cells and mediated by bi-directional cell contact and secretion of cytokines, which both sustain and invigorate the tumor and suppress immunity. CLL treatment generally makes the immunodeficiency worse (Hamblin & Hamblin, 2008). The proportion of patients treated with purine analogs and monoclonal antibodies such as rituximab and alemtuzumab is increasing. As a result of this therapy, these patients often experience profound and sustained T-cell immunodeficiency. Consequently, the spectrum of organisms causing infections in these patients is changing from common bacterial organisms to less common opportunistic pathogens such as Pneumocystis, Listeria, mycobacteria, herpesviruses and Candida (Wadhwa & Morrison, 2006). The early recognition of infections as well as prophylactic administration of appropriate antibiotics has been the mainstay of managing infections inpatients with CLL. Hopefully, increasing understanding of the molecular events underlying the neoplastic change in CLL will lead to more targeted and less immunosuppressive therapeutic modalities (Ravandi & O'Brien S, 2006).