Functions and structures of epithelial cells vary, depending upon their locations in organs/tissues. Pathophysiological responses of epithelia are associated with challenges, severities, durations and diseases. Epithelial proteomics has been used to understand the role of these cells in the pathogenesis of several diseases, and has the potential to identify novel biomarkers for disease prognosis, diagnosis and therapies. Epithelial brush border membranes (BBMs) are involved in digestion, absorption, metabolism, and transport of nutrients and drugs, clearance of and defense against toxins, and initiation of intracellular signaling and maintenance of cellular structural integrity. The present article review proteomic research on epithelial brush borders to understand the potential links among the function and disease associations of epithelial BBM proteomics. We found that the amount and functional ratio of epithelial cell BBM proteomic profiles obviously vary among species, cell locations, organ functions, research groups, and methodologies utilized. Many of these proteins may be identified and their functions elucidated, probably providing potential new markers for epithelial-associated diseases and potential therapeutic targets. There is still a great need for proteomic studies for analysis and comparisons of BBM protein profiles associated with normal physiological and pathophysiological states, organ function and dysfunction, and clinical health and disease.