OBJECTIVES: Health-care acquired infections (HCAIs) and resulting antibiotic treatments have been raising global concerns. HCAIs represent a substantial economic and humanistic burden with increasing costs, morbidity and mortality. Concerns around antibiotic use include resistance and lack of new products to market. The latter is related to difficulty in gaining approval, potential lack of profitability, complicated market assess, and difficulty in demonstrating value. Methods used for economic evaluations may contribute to the difficulty in assessing antibiotics. Our objective was to review published economic evaluations of antibiotics in HCAIs and to summarize currently used methods and challenges in assessing cost-effectiveness.  METHODS: We conducted a MEDLINE search for model-based, health economic evaluations of antibiotics in the six most prevalent HCAIs in the UK (respiratory tract, urinary tract, surgical site, clinical sepsis, gastrointestinal and bloodstream infections). Original, English language studies were included. Among others, analysis type, model structure, perspective, time horizon and outcomes were extracted.  RESULTS: We identified 126 papers, of which 19 met the inclusion criteria. These included 13 cost-effectiveness, four cost-consequence, one cost-minimization and one cost-benefit analyses. Of the models 12 were decision trees/decision models, three cost-calculators, one Markov model and one discrete even simulation. 2 papers did not report sufficient methodology. Time horizons were mainly the length of an infection.  Main outcomes were cost-per cure, cost-per patient treated, cost-per QALY and total cost saving. Economic models tend not to account for changes in prevalence of resistance, and additional potential benefits such as preventing transmission of resistance.   CONCLUSIONS: Most identified economic evaluations were simplistic, using cost-effectiveness approach through a simple decision tree, over short time-horizon, with payer perspective. This limits the flexibility of the evaluations to account for benefits of antibiotics in addressing burden of HCAIs and the current global concerns, contributing to the difficulty of assessing economic benefit of antibiotics.