Central nervous system (CNS) infections are the main cause of seizures and acquired epilepsy in the developing world. Geographical variations determine the common causes in a particular region. Acute seizures are common in severe meningitis, viral encephalitis, malaria, and neurocysticercosis, and in most cases are associated with increased mortality and morbidity, including subsequent epilepsy. Neuronal excitability secondary to proinflammatory signals induced by CNS infections are an important common mechanism for the generation of seizures, in addition to various other specific mechanisms. Newer insights into the neurobiology of these infections and the associated epilepsy could help in developing neuroprotective interventions. Management issues include prompt treatment of acute seizures and the underlying CNS infection, correction of associated predisposing factors, and decisions regarding the appropriate choice and duration of antiepileptic therapy. Strategies for the prevention of epilepsy in CNS infections such as early anti-infective and anti-inflammatory therapy need scientific exploration. Prevention of CNS infections is the only definitive way forward to reduce the burden of epilepsy in developing countries.