With improved therapies, patients with cancer survive longer. However, both the acute complications of intensive therapies and the risks of chronic immunosuppression have led to an increased incidence of central nervous system (CNS) infections. The presentation and course of common infections may be different from those in patients without cancer, and new syndromes related both to the underlying diseases and to their treatment have complicated the differential diagnosis. Noninfectious disorders such as drug treatment complications, vascular lesions, and radiation effects can mimic CNS infections. The major clinical presentations of CNS infections can be divided into meningoencephalitic syndromes and deficits due to focal mass lesions. The range of pathogens can be narrowed by considering the type of immune deficit present. The two groups of patients who most frequently develop CNS infections are those undergoing procedures for primary brain tumors and hematopoietic stem cell transplant recipients. Among several recently recognized syndromes in the latter are infections due to human herpesviruses 6 and 7, West Nile virus, and the immune reconstitution inflammatory syndrome.