Keratoconus is a bilateral noninflammatory corneal ectasia with an incidence of approximately 1 per 2,000 in the general population. It has well-described clinical signs, but early forms of the disease may go undetected unless the anterior corneal topography is studied. Early disease is now best detected with videokeratography. Classic histopathologic features include stromal thinning, iron deposition in the epithelial basement membrane, and breaks in Bowman's layer. Keratoconus is most commonly an isolated disorder, although several reports describe an association with Down syndrome, Leber's congenital amaurosis, and mitral valve prolapse. The differential diagnosis of keratoconus includes keratoglobus, pellucid marginal degeneration and Terrien's marginal degeneration. Contact lenses are the most common treatment modality. When contact lenses fail, corneal transplant is the best and most successful surgical option. Despite intensive clinical and laboratory investigation, the etiology of keratoconus remains unclear. Clinical studies provide strong indications of a major role for genes in its etiology. Videokeratography is playing an increasing role in defining the genetics of keratoconus, since early forms of the disease can be more accurately detected and potentially quantified in a reproducible manner. Laboratory studies suggest a role for degradative enzymes and proteinase inhibitors and a possible role for the interleukin-1 system in its pathogenesis, but these roles need to be more clearly defined. Genes suggested by these studies, as well as collagen genes and their regulatory products, could potentially be used as candidate genes to study patients with familial keratoconus. Such studies may provide the clues needed to enable us to better understand the underlying mechanisms that cause the corneal thinning in this disorder.