Corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A (UVA) light has become a viable treatment for keratoconus. In cases in which corneal transplant may have previously been a patient's primary treatment option, the results of CXL have varied from decreased progression of the disease to marked regression characterized by improvement in visual acuity. In addition, changes to the original protocol have been tested that include leaving the epithelium intact and increasing the UVA intensity while decreasing the exposure time. The variation in results and protocols underscores the need for a greater understanding of the procedure and its effects. Ideally, a complete definition of the effects of CXL will lead to patient-specific treatment through highly controlled delivery methods of riboflavin and UVA light and complete mathematical models for predicting the final shape and refractive effect of the cornea. Thus, in this review, we aimed to describe the current techniques for measuring the effect of CXL, with a focus on material property changes, while highlighting the challenge of engineering a predictable mathematical model of the procedure and the resulting clinical outcome.