Myopia represents a failure of the normal process of emmetropization, which is essentially endogenous to the eye. Emmetropization involves defocus detection at the level of the amacrine and bipolar cells of the outer retina, diffusion of a signal or signals across the retinal pigment epithelium and choroid, and alteration of the scleral matrix, likely through modulation of proteoglycan synthesis. Elucidating and effectively bolstering the deficient steps in this regulatory pathway would mark a significant advance given myopia's tremendous impact. Clinical experience, longitudinal studies, epidemiological data and numerous animal experiments have enhanced our understanding of myopia. Interpretation of the epidemiological data is often complicated by the difficulties of distinguishing environmental from genetic influences, especially those pertaining to slow developmental changes. Likewise, it is important that the animal models be interpreted with an appreciation that the human eye varies structurally and developmentally from that of other species. Studies of the chick eye have formed the basis for several hypotheses of myopic development, but the chick does not possess a fovea or retinal blood supply. It is unclear whether these differences alter the pathways of emmetropization. Even closely related primate species can exhibit different responses to form deprivation conditions, suggesting differing mechanisms of eye growth control. Monocular occlusion of the rhesus macaque, for instance, results in myopia when the ciliary muscle is paralyzed or the optic nerve cut, but does not in the stumptailed macaque, suggesting a role of excessive accommodation in the development of myopia in the stumptail but not the rhesus [36]. Given such variability in the models a persisting element of continued myopia research must be an evaluation of the relevance of any given model to the human condition. In this regard, the study of changing patterns of gene expression within and among species during emmetropization and myopic progression may offer a productive avenue for future research.