Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness in the elderly. Successful therapy is not yet available for the majority of patients, especially not for patients with dry AMD. AMD at cellular and molecular levels is at least in part a microcirculatory disorder of the retina. Rheopheresis is a safe and effective modality of therapeutic apheresis to treat microcirculatory disorders and represents a novel treatment option for patients with dry AMD. Elimination of a defined spectrum of high molecular weight proteins from human plasma including pathophysiologically relevant risk factors for AMD such as fibrinogen, cholesterol, von Willebrand factor, and alpha 2-macroglobulin results in the reduction of blood and plasma viscosity as well as erythrocyte and thrombocyte aggregation. Pulses of lowering blood and plasma viscosity performed as a series of Rheopheresis treatments lead to rapid changes of blood flow, subsequently inducing sustained improvement of microcirculation and recovery of retinal function. Two controlled randomized clinical trials demonstrated the safety and efficacy of Rheopheresis for the treatment of AMD patients, especially for those with the dry form. Recently the interim analysis of the sham-controlled, double blind, randomized multicenter Multicenter Investigation of Rheopheresis for AMD (MIRA-I) trial confirmed these results. The framework of completed and still ongoing controlled clinical trials in combination with postcertification studies including the RheoNet registry represents a comprehensive quality management approach for this novel interdisciplinary therapy for AMD. The development and continuous update of guidelines for the precise indication of Rheopheresis for AMD follows the requirements of evidence-based medicine.