Developments in the field of tear film protein profiling are reviewed, including the advantages and disadvantages of the multiplex bead array technique and its potential for identifying biomarkers of ocular surface disease. Commercial kits, which specifically employ 96-well plates with polystyrene microspheres and magnetic beads, and sensitivity variations between them are discussed. Modifications to protocols of these kits (which are designed primarily for larger sample volumes, such as blood and cell culture supernatants) may be necessary for tear fluid samples. Multiplex bead array is compared to the "gold standard," ELISA. The challenges of diagnosing and monitoring dry eye disease, due to the conflicting and variable signs and symptoms presented, are illustrated by the authors' own study results. The development of a biomarker profile for the disease would be a useful approach to the ongoing problems of diagnosis. The multiplex bead array technique has important potential applications in this regard.