This chapter discusses the diagnosis, evaluation and management of meningitis and encephalitis. The differential diagnosis for meningitis and encephalitis includes subarachnoid hemorrhage, dural sinus thrombosis, metabolic encephalopathy, and other infections not involving the central nervous system (CNS). If bacterial meningitis is suspected, the patient should be isolated. Laboratory evaluations should include complete blood count, chemistries, blood cultures, serum lactate, and coagulation profile. High index of suspicion is important for meningitis and encephalitis, and a lumbar puncture (LP) should be considered in patients with fever and altered mental status without an identified source of infection. Patients at risk for intracranial pathologies such as central nervous system (CNS) mass lesions or with signs of increased intracranial pressure should undergo a computed tomography (CT) scan of the head prior to lumbar puncture. Lumbar puncture with evaluation of the cerebrospinal fluid (CSF) is the diagnostic test of choice.