Collagen corneal cross-linking (CXL) is an invasive pharmacological treatment strategy used for corneal ectatic disorders and is currently the only treatment capable of halting the progression of the disease. In the past 20 years, the conservative management of progressive corneal ectasia has changed, thanks to this procedure that produces strengthening of the corneal tissue through the photochemical reaction generated by the combined action of riboflavin and ultraviolet A radiation. Many modified protocols have been implemented to halt the progression of the disease and to delay or prevent visual loss and surgical procedures such as corneal transplantation. Because of the variety of different protocols that are currently used, the results that are being reported are very variable, and could generate some confusion in relation to the true efficacy of the procedure. The aim of this review was to provide an overview of the aforementioned protocols that are designed to maintain the efficacy of CXL in halting the progression of the disease but avoiding the major limitations of the procedure.