Isolation of antimicrobial-resistant microbes from ocular infections may be becoming more frequent. Infections caused by these microbes can be difficult to treat and lead to poor outcomes. However, new therapies are being developed which may help improve clinical outcomes. This review examines recent reports on the isolation of antibiotic-resistant microbes from ocular infections. In addition, an overview of the development of some new antibiotic therapies is given. The recent literature regarding antibiotic use and resistance, isolation of antibiotic-resistant microbes from ocular infections and the development of potential new antibiotics that can be used to treat these infections was reviewed. Ocular microbial infections are a global public health issue as they can result in vision loss which compromises quality of life. Approximately 70 per cent of ocular infections are caused by bacteria including Chlamydia trachomatis, Staphylococcus aureus, and Pseudomonas aeruginosa and fungi such as Candida albicans, Aspergillus spp. and Fusarium spp. Resistance to first-line antibiotics such as fluoroquinolones and azoles has increased, with resistance of S. aureus isolates from the USA to fluoroquinolones reaching 32 per cent of isolates and 35 per cent being methicillin-resistant (MRSA). Lower levels of MRSA (seven per cent) were isolated by an Australian study. Antimicrobial peptides, which are broad-spectrum alternatives to antibiotics, have been tested as possible new drugs. Several have shown promise in animal models of keratitis, especially treating P. aeruginosa, S. aureus or C. albicans infections. Reports of increasing resistance of ocular isolates to mainstay antibiotics are a concern, and there is evidence that for ocular surface disease this resistance translates into worse clinical outcomes. New antibiotics are being developed, but not by large pharmaceutical companies and mostly in university research laboratories and smaller biotech companies. Antimicrobial peptides show promise in treating keratitis.