PURPOSE. To define the three-dimensional topologic organization of the human peripapillary capillary plexuses in order to better understand the hemodynamic characteristics of this retinal circulation. METHODS. The retinal microvasculature was perfusion labeled in five normal human donor eyes, and optical stacks were collected from regions immediately superior, temporal, inferior, and nasal to the optic disk by using confocal scanning laser microscopy. The spatial location and morphometric characteristics of capillary plexuses were compared. Three-dimensional visualization strategies were used to document the organization of vascular conduits that interconnect capillary beds and to study the communications between capillary beds and precapillary arterioles and postcapillary venules. RESULTS. The peripapillary microcirculation is composed of four capillary plexuses, including the radial peripapillary capillary plexus at the level of the nerve fiber layer, the superficial capillary plexus (SCP) at the level of the ganglion cell layer, the intermediate capillary plexus located at the inner boundary of the inner nuclear layer, and the deep capillary plexus located at the outer boundary of the inner nuclear layer. Capillary diameter and density were significantly different between the four plexuses (both P ≤ 0.011). The SCP is the only capillary bed that receives feeding and draining branches directly from precapillary arterioles and postcapillary venules, respectively. Four different inflow and outflow patterns characterized the communication between the SCP and surrounding capillary beds. CONCLUSIONS. The capillary plexuses of the human peripapillary microcirculation are arranged in series and parallel and manifest specializations that likely reflect the unique metabolic demands and biochemical environment of the retinal layers.