The study of the aqueous humor (AH) plays a key role in understanding the pathophysiology of glaucoma. The AH provides nutrition, maintains the appropriate intraocular pressure, and provides important information about the mechanisms of the disease. The development of modern technologies has allowed the use of more accurate analytical methods, which has proven to be a key factor in determining the changes occurring in the proteome of the aqueous humor of glaucoma patients. Recently, researchers have observed changes in the levels of proteins associated with inflammation, oxidative stress, the complement system, and extracellular matrix remodeling. They have also shown that these changes may be variable for different types of glaucoma. The objective of this review is to collect and summarize the current knowledge on the potential biomarkers and pathomechanisms involved in the pathogenesis of glaucoma. We hope that our review will contribute to the improvement of current diagnostic methods in this illness and, through a better understanding of the changes occurring during the progression of the disease, will enable the development of more effective preventive and therapeutic strategies in the future.