Genetic mutation can result in insignificant corneal changes that can simply be incidental findings on exam or can result in defects of enormous visual consequence. The more substantial phenotypes tend to be secondary to mutations that cause changes in gene expression early in embryogenesis. Less devastating mutations are those that cause a slow degeneration over time. In this chapter we will explore both ends of the spectrum and will discuss each disease entity in detail including presenting signs and symptoms as well as the genes responsible for each. We will also highlight corneal diseases that express variability in penetrance as well as those that exhibit allelic and locus heterogeneity.