Purpose: To identify, characterize, and discuss the current technological status of in vivo comeal diagnostic imaging and target high-priority future development needs. Methods: In vivo tandem scanning microscopy (non-coherent), scanning slit confocal microscopy (non-coherent), and laser scanning confocal microscopy (coherent) are examined. The current and future roles of multi-photon and higher order harmonic imaging are also discussed. Results and Conclusions: This keynote review demonstrates the current abilities and limitations of three currently used clinical imaging modalities to resolve the cellular and structural layers of the cornea temporally and spatially in three or four dimensions (x, y, z, t), with applications to the study of clinical-pathological processes such as inflammation; infection, wound healing, drug toxicity, organ development, differentiation and effects of genetic diseases. Each of these approaches has strengths and weaknesses. Thus, future technological development is essential to provide exciting new insights into understanding the structure and function of not only the cornea and the other ocular structures, but also other multicellular organs in health and disease. These imaging paradigms are among the most important advances in medical science in the past three decades.