This chapter begins with important CNS infections, which are broken down into viral, bacterial, and fungal. The most important causes are first discussed, including herpes simplex virus, Human herpes virus 6, and HIV encephalitis, with their findings on CT and MRI. The review of HIV also includes a discussion of progressive multifocal leukoencephalopathy. Review of additional Flaviviridae infections like Japanese and tick-borne encephalitis follows due to their importance in Asia and Europe, respectively. The chapter then leans into MRI for distinguishing cerebritis from encephalitis, diagnosing subdural empyema and intraparenchymal abscess, recognizing ventriculitis, and finding evidence of meningitis. This section concludes with examples of unusual/opportunistic infections like tuberculosis meningitis and a brief discussion of prions. The second section reviews demyelinating and inflammatory CNS diseases. A thorough discussion of MS begins the section, including the 2024 McDonald Criteria. Imaging distinctions between MS, NMO, and MOGAD are explored with MRI examples provided. Additional common demyelinating disorders like Guillain-Barré syndrome and ADEM are reviewed. This section is concluded with information about CNS vasculitis, neurosarcoidosis, and neuro-Behcet’s disease. The chapter concludes with toxic encephalopathy findings on MRI, including ethanol, methanol, ethylene glycol, opioid, and carbon monoxide poisoning, methotrexate toxicity, and hepatic encephalopathy.