Biomarkers are central to the translational medicine strategic focus, though strict criteria need to be applied to their designation and utility. They are one of the most promising areas of medical research, but the "biomarker life-cycle" must be understood to avoid false-positive and false-negative results. Molecular biomarkers will revolutionize the treatment of neurological diseases, but the rate of progress depends on a bold, visionary stance by neurologists, as well as scientists, biotech and pharmaceutical industries, funding agencies, and regulators. One important tool in studying cell-specific biomarkers is multiparameter flow cytometry. Cerebrospinal fluid immunophenotyping, or immune phenotypic subsets, captures the biology of intrathecal inflammatory processes, and has the potential to guide personalized immunotherapeutic selection and monitor treatment efficacy. Though data exist for some disorders, they are surprisingly lacking in many others, identifying a serious deficit to be overcome. Flow cytometric immunophenotyping provides a valuable, available, and feasible "window" into both adaptive and innate components of neuroinflammation that is currently underutilized.