Infectious ocular surface disease (IOSD) is a common problem in shelter‐housed domestic cats and has a widespread negative impact on animal welfare. While the common etiological agents are well‐described, addressing IOSD in large groups of animals presents a management challenge to the clinician and logistical challenges to shelter employees. Treatments, diagnostics, and prevention strategies that are effective in privately owned or experimental animals may be impractical or ineffective in the shelter environment. This review article focuses on the relative prevalence of etiological agents in feline IOSD, practical diagnostic testing protocols, prevention strategies, and treatment of IOSD in shelter‐housed cats. Discrepancies between experimental laboratory‐based studies and clinical trials assessing therapeutics for treatment of feline herpes virus are highlighted. Further high‐quality clinical trials are necessary to determine optimal preventative and therapeutic protocols for IOSD in shelter‐housed cats.