The first detailed descriptions of keratoconus were published exactly 150 years ago in the original work of Dr John Nottingham, bringing a degree of clarity to a previously confusing clinical phenomenon – further supported by observations of other contemporaries in the field such as Sir William Bowman. However, it would be another 100 years before knowledge of keratoconus would grow substantially; indeed, our current level of understanding is primarily a result of extensive clinical and laboratory research conducted over the last 50 years – particularly based upon the enormous technological advances of the last two decades. Large clinical studies have confirmed that keratoconus is a non-inflammatory corneal disease with central or paracentral corneal thinning, which exhibits progressive corneal steepening and protrusion that typically results in increasing regular and thereafter irregular astigmatism. Ultimately, disease progression may lead to corneal scarring, corneal hydrops and loss of best spectacle-corrected visual acuity. Although visual rehabilitation may be effected by expert contact lens fitting, 20% of subjects may require corneal transplantation. This Gregg lecture provides a highly referenced, wide-ranging overview of both historical and contemporary aspects of keratoconus, including diagnostic, phenotypic and prognostic factors revealed by large clinical studies, critical diagnostic advances enabled by Placido and slit-scanning computerized corneal topography, the emerging roles of higher order aberration wave-front analysis and corneal hysteresis in delineating early and subclinical keratoconus, inheritance and genetic predisposition to keratoconus, corneal microstructural changes unveiled by in vivo confocal microscopy, unifying theories to explain associations between keratoconus, atopy, eye rubbing and keratocyte apoptosis, and surgical options for keratoconus, such as corneal transplantation, intrastromal ring segments, collagen cross-linking and keratocyte transplantation. However, 150 years along the path our knowledge of keratoconus remains incomplete, but technological advances should enable us to put together the final pieces of the jigsaw in the foreseeable future.