Infectious complications continue to be a major cause of morbidity and mortality in patients with chronic lymphocytic leukaemia (CLL). The pathogenesis of infections in these patients is multifactorial, related to inherent immune defects and therapy-related immunosuppression. Hypogammaglobulinaemia is an important predisposing factor for infection in all patients. The use of the purine analogues such as fludarabine, and monoclonal antibodies such as rituximab and alemtuzumab, has introduced a new spectrum of infectious complications caused by pathogens such as Pneumocystis, Listeria, mycobacteria, herpesviruses Candida and Aspergillus, related to the cellular immune suppression induced by these agents. This review focusses on the pathogenesis and risk factors for infections in patients with CLL, the spectrum of infectious complications and preventive approaches to infection in these patients, using antimicrobial and immunoglobulin prophylaxis and vaccination strategies.