Although outnumbered more than 20:1 by rod photoreceptors, cone cells in the human retina mediate daylight vision and are critical for visual acuity and color discrimination. A variety of human diseases are characterized by a progressive loss of cone photoreceptors but the low abundance of cones and the absence of a macula in non-primate mammalian retinas have made it difficult to investigate cones directly. Conventional rodents (laboratory mice and rats) are nocturnal rod-dominated species with few cones in the retina, and studying other animals with cone-rich retinas presents various logistic and technical difficulties. Originating in the early 1900s, past research has begun to provide insights into cone ultrastructure but has yet to afford an overall perspective of cone cell organization. This review summarizes our past progress and focuses on the recent introduction of special mammalian models (transgenic mice and diurnal rats rich in cones) that together with new investigative techniques such as atomic force microscopy and cryo-electron tomography promise to reveal a more unified concept of cone photoreceptor organization and its role in retinal diseases.