Primate models of cystoid macular edema (CME) were developed along four sets of presumed primary causative factors: 1) disruption of the blood-retinal barrier at the retinal vasculature and the retinal pigment epithelium; 2) ischemic tissue injury with cyst formation; 3) intraocular events frequently observed in patients with CME, such as inflammation, ocular hypotony, and vitreous traction; and 4) the probable additive effect on the macula by systemic diseases such as diabetes mellitus and systemic hypertension. While each experiment produced some aspects of CME in the human, none gave the complete picture. It is concluded that CME is the final common pathway of a multifactorial syndrome.