Keratoconus is a progressive, non-inflammatory corneal ectasia characterized by stromal thinning and conical protrusion. Corneal collagen cross-linking (CXL) remains the only proven treatment to halt its progression. This review compares the mechanisms, efficacy, and safety of standard (Dresden), accelerated, and transepithelial (including iontophoretic) protocols, with particular emphasis on pediatric keratoconus. Studies from PubMed, Scopus, and Web of Science were comprehensively reviewed. Standard CXL remains the gold standard due to its strong biomechanical effect and long-term stability. Accelerated protocols reduce treatment time while maintaining comparable outcomes in selected patients, though the stiffening effect may be shallower. Transepithelial and iontophoretic approaches improve comfort and reduce complications but show reduced efficacy. Future perspectives include oxygen supplementation, customized fluence modulation, and pharmacologic enhancers to improve riboflavin diffusion and oxygen availability.