Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system, often emerging in early adulthood and representing a leading cause of neurological disability in young adults. Diagnosing MS involves a combination of clinical assessment, imaging and laboratory tests, with cerebrospinal fluid (CSF)-specific immunoglobulin G (IgG) oligoclonal bands (OCB) being an important marker for fulfilling the dissemination in time criteria. A recent survey of Canadian clinical laboratories highlighted considerable variation in OCB reporting practices nationwide, spanning quality control (QC) practices, acceptable time limits between paired CSF and serum sample collections, protocols for reporting band counts, interpretation and reporting of mirrored patterns, testing panels, and interpretive thresholds. These inconsistencies impact patient care and the comparability of laboratory results across different laboratories. The Harmonized CSF Analysis for MS Investigation (hCAMI) subcommittee of the Canadian Society of Clinical Chemists Reference Interval Harmonization Working Group was established to generate recommendations for laboratory processes and reporting of CSF OCB and associated tests supporting MS diagnosis. This review serves as a foundation for these efforts, summarizing the available evidence in areas where practice variations have been noted. This review begins by examining current practices and guidelines for standardized quality assurance, including optimal QC materials, frequency, documentation, and participation in external quality assurance programs. The disparity between paired CSF and serum sample acceptability time limits was further examined by reviewing current practices and recommendations as well as compiling evidence on IgG synthesis, turnover rate, biological variation, and stability in CSF and serum samples. Additionally, this review addresses the lack of consensus on reporting the number of CSF-specific and CSF-serum matched bands, focusing on interpreter variability and clinical utility. Contributing factors and clinical implications of mirror patterns, including discussion on monoclonal gammopathies and cases of matched bands of differing staining intensity, is provided. Testing panel components including adjunctive CSF tests, such as the IgG index, to support MS investigations despite their absence from clinical guidelines is also discussed. This review also provides a comprehensive analysis of current practices, guidelines, and the evidence surrounding different cutoffs for IgG index and CSF-specific bands. Finally, the review considers emerging biomarkers, such as the kappa free light chain index and serum neurofilament light chain, which show promise for MS diagnosis and management. This comprehensive review of current practices, guidelines, and evolving evidence will guide the hCAMI subcommittee’s efforts to harmonize CSF OCB analysis and improve MS diagnosis.