OBJECTIVES:   To review economic evidence supporting Rx-to-OTC switches. METHODS:   A systematic search of the EMBASE, Pubmed, ISPOR conference abstracts databases and industry associations websites was conducted.  The search was limited to years 2000–2010 and to North America and European countries.  Two independent reviewers selected eligible studies.   RESULTS: The search identified 14 reviews, 12 model publications, 12 database analyses, 5 prospective observational studies and 11 other.  Most articles originated from the US.  In 5/6 database analyses and in 8/9 budget impact models (BIM) that quantified cost consequences of Rx-to-OTC switching, it was shown to generate savings to healthcare budget holders, mainly due to Rx-drug acquisition savings.  Other key direct savings included avoided: doctor’s visits to obtain a prescription; emergency room visits or hospitalisations due to easier access to an effective or safer therapy.  Employers’ benefits included less time-off work to obtain a prescription and less absenteeism and presenteeism due to easier access to therapies that improve employee productivity.  Cost consequences of potential misuse due to lack of doctor’s supervision were frequently acknowledged but rarely quantified.  The key factors determining the extent of savings were: uptake rates of the OTC drug among different types of populations (i.e. those on Rx drugs, other Rx drugs, OTC-treated, untreated and undiagnosed), therapeutic area and presence of disreimbursement policies.  The only European BIM is old (2004) and showed potential annual savings of €16.4 billion, assuming that 5% of Rx drugs are switched to the OTC status.  However, its use is limited as it is not specific to any drug/disease area and took a simplistic approach to costing and uptake among populations considered. CONCLUSIONS: Rx-to-OTC switches are a real opportunity to realise savings for budget holders and productivity gains for employers.   More robust economic models are required to estimate the impact of the switches in Europe.