Meningitis and Encephalitis are associated with high rates of mortality and neurological sequelae. The differential diagnosis includes a wide spectrum of infectious and non-infectious etiologies, some requiring urgent therapy for survival. The current management challenges in patients with meningitis and encephalitis include a low sensitivity of meningeal signs, overutilization of unnecessary screening cranial imaging, delays in diagnosis of urgent treatable causes, a large proportion of unknown etiologies, low sensitivity of current microbiological techniques especially in the setting of previous antibiotic therapy, underutilization of available molecular diagnostic tests, and empiric antibiotic therapy and hospitalization for viral meningitis cases. Even though there are published guidelines, compliance with them is not optimal and physicians do not follow standardized algorithms in their empirical approach.