INTRODUCTION: Chloramphenicol is a broad-spectrum antibiotic widely used for treating ophthalmic infections, but concerns about rising bacterial resistance to chloramphenicol have been observed due to its frequent use as an over-the-counter medication. This review assessed the common ophthalmic bacterial pathogens, their chloramphenicol resistance mechanisms, and rates of drug resistance. METHODS: PubMed and Google Scholar databases were searched for relevant publications from the years 2000 to 2022, bordering on ophthalmic bacterial infections, chloramphenicol susceptibility profiles, and drug resistance mechanisms against chloramphenicol. A total of 53 journal publications met the inclusion criteria, with data on the antibiotic susceptibility profiles available in 44 of the reviewed studies, which were extracted and analyzed. RESULTS: The mean resistance rates to chloramphenicol from antibiotic susceptibility profiles varied between 0% and 74.1%, with the majority of the studies (86.4%) showing chloramphenicol resistance rates below 50%, and more than half (23 out of 44) of the studies showed resistance rates lower than 20%. The majority of the publications (n = 27; 61.4%) were from developed nations, compared to developing nations (n = 14; 31.8%), while a fraction (n = 3; 6.8%) of the studies were regional cohort studies in Europe, with no country-specific drug resistance rates. No pattern of cumulative increase or decrease in ophthalmic bacterial resistance to chloramphenicol was observed. CONCLUSIONS: Chloramphenicol is still active against ophthalmic bacterial infections and is suitable as a topical antibiotic for ophthalmic infections. However, concerns remain about the drug becoming unsuitable in the long run due to some proof of high drug resistance rates.