With improved treatments, patients with many types of cancer survive longer. However, both the acute adverse effects of more intensive therapies and the risks of chronic immunosuppression have led to a diverse and evolving spectrum of central nervous system (CNS) infections. The presentation and course of CNS infections in cancer patients may be different from those in patients without cancer, complicating and delaying accurate diagnosis. New syndromes related both to the underlying malignancies and to their treatment continue to emerge. Noninfectious disorders such as adverse drug effects, vascular lesions, and radiation effects can mimic CNS infections. The two major clinical presentations of CNS infections are meningoencephalitic syndromes and focal deficits due to mass lesions. The range of pathogens can be narrowed by considering the type of immune deficit present, local nosocomial trends, and the specific vulnerabilities created by the underlying disease and treatment regimen. Patients undergoing neurosurgical procedures and those receiving hematopoietic cell transplants (HCT) account for the majority of cancer patients with CNS infections. Significant recent changes reviewed here include evolving patterns of bacterial meningitis, current treatment recommendations for fungal infections, special infectious risks associated with immunomodulatory therapies, and neuroimaging techniques to distinguish infection from other intracranial processes.