Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder of the central nervous system that is specifically associated with demyelination of spinal cord and optic nerves. The discovery of specific autoantibody markers such as aquaporin-4 IgG and myelin oligodendrocyte glycoprotein IgG has led to several methodologies being developed and validated. There have been numerous investigations of the clinical and radiological presentations used in the clinical diagnosis of NMOSD. However, although various laboratory diagnostic techniques have been standardized and validated, a gold-standard test has yet to be finalized due to uncertain sensitivities and specificities of the methodologies. For this review, the literature was surveyed to compile the standardized laboratory techniques utilized for the differential diagnosis of NMOSD. Enzyme-linked immunosorbent assays enable screening of NMOSD, but they are considered less sensitive than cell-based assays (CBAs), which were found to be highly sensitive and specific. However, CBAs are laborious and prone to batch variations in their results, since the expression levels of protein need to be maintained and monitored meticulously.Standardizing point-of-care devices and peptide-based assays would make it possible to improve the turnaround time and accessibility of the test, especially in resource-poor settings.