Confocal microscopy enables microstructural analysis of the in vivo cornea, allowing fresh insight into corneal microstructure in health, and in inherited and acquired corneal disease. This method of corneal examination is evolving in an exponential fashion, with rapid advances in technology being mirrored by rapid growth in both research and clinical applications. Whilst initially the evidence base for in vivo confocal microscopy consisted largely of small case studies, in recent years there has been a trend towards collecting quantitative data in an effort to better delineate between heath and disease. Confocal microscopy has been utilised clinically to aid in the diagnosis of infectious keratitis, in particular Acanthamoeba and fungal keratitis, and has also established a role in the diagnosis and phenotyping of corneal dystrophies. This article reviews in vivo confocal microscopy of the human cornea in health and disease and examines clinical and research applications of this new technology.