Evaluating gene expression changes presents one of the most powerful interrogative approaches to study the molecular, biochemical, and cellular pathways associated with glaucomatous disease pathology. Technologies to study gene expression profiles in glaucoma are wide ranging. Qualitative techniques provide the power of localizing expression changes to individual cells, but are not robust to evaluate differences in expression changes. Alternatively, quantitative changes provide a high level of stringency to quantify changes in gene expression. Additionally, advances in high throughput analysis and bioinformatics have dramatically improved the number of individual genes that can be evaluated in a single experiment, while dramatically reducing amounts of input tissue/starting material. Together, gene expression profiling and proteomics have yielded new insights on the roles of neuroinflammation, the complement cascade, and metabolic shutdown as important players in the pathology of the optic nerve head and retina in this disease.