The economic burden of influenza-related illness has been estimated to be 71.3-166 billion US dollars in the US, the majority of which is attributable to indirect costs as a result of lost productivity. There are currently four antiviral drugs available for the treatment of influenza: two ion channel blockers, amantadine and rimantadine; and two neuraminidase inhibitors, zanamivir and oseltamivir. The objective of this paper was to review the studies evaluating the cost effectiveness of currently available antiviral treatment and prophylaxis management strategies for influenza. Published studies that reported both costs and effectiveness of influenza management were extracted using MEDLINE, pre-MEDLINE and EMBASE. To facilitate a broad comparison, all costs were inflated to 2003 US dollars. Fifteen studies met the inclusion criteria of the review, with 14 analyses based on decision-analytic modelling and one economic analysis performed alongside a clinical trial. Management strategies included antiviral influenza prophylaxis or vaccination, empiric treatment of suspected disease, or antiviral treatment following rapid influenza testing. Study populations included healthy adults, adults at risk of influenza-related adverse outcomes, institutionalised and non-institutionalised elderly, and children. The comparator in all studies was standard care (i.e. over-the-counter medications only), and analyses were carried out from both the societal and payer perspectives. The only dominant strategy relative to standard care was vaccination of the institutionalised elderly. All other strategies in all populations were both more costly and more effective than standard care. Depending on the population and the perspective, the incremental cost-effectiveness ratios (ICERs) for antiviral treatment strategies ranged from 5000 US dollars/QALY for amantadine in test-and-treat studies to >400,000 US dollars/QALY for zanamivir or oseltamivir treatment in children. Sensitivity analysis in all studies consistently reported a strong influence of the population prevalence or diagnostic accuracy of influenza on the cost effectiveness of all strategies. Baseline influenza prevalence varied widely between studies, ranging from 15% to 68%. There was also a wide variation in the assumption about the disutility of influenza (ranging from -0.137 to -0.983 for the elderly requiring hospitalisation), which also impacted the cost effectiveness. Given the variation in the ICERs of antiviral treatment and prophylaxis, the uncertainty around many model parameters, and the dynamic nature of influenza from year to year, one can only conclude that antiviral treatment or prophylaxis for influenza is likely to be more cost effective in specific populations at specific times during the influenza season, and during influenza seasons when the population prevalence reaches epidemic levels or there is mismatch between the vaccine and the circulating virus.