Multidrug-resistant bacterial keratitis poses a serious threat to vision. In recent years, as pathogens have become increasingly resistant to antibiotics, complications such as corneal melting and perforation may still occur even when bacterial keratitis (BK) is diagnosed and treated promptly. Therefore, it is critical to explore new therapeutic approaches to combat the growing challenge of drug-resistant infectious keratitis. Corneal collagen cross-linking (CXL), originally established for the treatment of keratoconus and post-refractive ectasia, has now been introduced as an adjunctive modality for infectious keratitis caused by multidrug-resistant organisms. To distinguish its application in infectious keratitis from that in ectatic disorders, CXL used for infectious keratitis has been termed photoactivated chromophore for infectious keratitis-corneal cross-linking (PACK-CXL). Current evidence indicates that PACK-CXL, as an adjunct to antibiotic therapy, is effective in treating BK. The therapeutic mechanisms of PACK-CXL and its clinical application in BK was summarized in this paper.