The cornea is a transparent, avascular and abundantly innervated tissue through which light rays are transmitted to the retina. The innermost layer of the cornea, also known as the endothelium, consists of a single layer of polygonal endothelial cells that serve an important role in preserving corneal transparency and hydration. The average corneal endothelial cell density (ECD) is the highest at birth (~3,000 cells/mm 2 ), which then decrease to ~2,500 cells/mm 2 at adulthood. These endothelial cells have limited regenerative potential and the minimum (critical) ECD required to maintain the pumping function of the endothelium is 400-500 cells/mm 2 . ECD < the critical value can result in decreased corneal transparency, development of corneal edema and reduced visual acuity. The condition of the corneal endothelium can be influenced by a number of factors, including systemic diseases, such as diabetes or atherosclerosis, eye diseases, such as uveitis or dry eye disease (DED) and therapeutic ophthalmological interventions. The aim of the present article is to review the impact of the most common systemic disorders (pseudoexfoliation syndrome, diabetes mellitus, cardiovascular disease), eye diseases (DED, uveitis, glaucoma, intraocular lens dislocation) and widely performed ophthalmic interventions (cataract surgery, intraocular pressure-lowering surgeries) on corneal ECD.