Multiple sclerosis (MS), a demyelinating disease of unknown etiology, is the most common cause of nontraumatic disabling neurologic disease of young and middle-aged adults in the United States. It is also one of the most difficult illnesses to define and characterize in neurologic practice. Until recently, neurologists had few laboratory tools to use in diagnosis. Today, however, technological breakthroughs in neurogenetics and laboratory methodologies are yielding useful assays for the clinical laboratory. The diagnosis of MS commonly is made on the basis of established clinical criteria. Although no specific laboratory diagnostic test exists, abnormalities in cerebrospinal fluid (CSF) help support the clinical diagnosis of MS. Careful correlation among laboratory data, clinical history, and imaging studies is necessary. This review describes the most common CSF abnormalities. This article is the first in a three-part continuing education series on neurology. Other articles will focus on stroke and neuropathy syndromes and antibodies.