OBJECTIVES: Despite the fact that short and long-term effects of the exposure to air pollution on health have been extensively analyzed, estimates of the healthcare economic impact of such effects are still limited. We therefore carried out a systematic review of the literature, with the aim of identifying the current major research focuses in the field and the topics that will need to be addressed in the future. METHODS: We searched the electronic databases MEDLINE and EMBASE, in which we applied respectively the following algorithms: 1) "(("cost of illness"[MeSH Terms] OR "health care costs"[MeSH Terms] OR "health expenditures"[MeSH Terms]) AND "environmental pollution"[MeSH Terms]) OR (Pollution[Title/Abstract] AND (Expenditure[Title/Abstract] OR Expenditures[Title/Abstract] OR cost[Title/Abstract] OR costs[Title/Abstract]) AND (health[Title/Abstract] OR healthcare[Title/Abstract]))"; 2) "‘health care cost'/exp AND 'pollution'/exp". Searches were limited to article written in English and Italian, without any date restriction. RESULTS: The initial selections identified 775 records in MEDLINE and 466 in EMBASE, 149 of which were classified as relevant. They focused on a wide range of pollutants, including volatile organic compounds, nitrogen dioxide, pesticides, ozone, particulate matter and tobacco smoke. Most of the studies assessed the health impact of environmental pollutants using direct and indirect cost estimates acquired from literature, mainly relying on cost of illness methods; 27 papers used an individual direct healthcare costs approach, but they usually didn’t involve indirect costs in the final computations. Finally, only a few studies distinguished between short-term and long-term effect of air pollution. CONCLUSIONS: The results of our review identified two main topics that deserve further research: future health impact assessments should integrate indirect costs estimates with information from the direct modeling of real-life healthcare costs; the short- and long-term economic impacts should be clearly separated.