Background: Since High Level Pharmaceutical Forum, several initiatives have been put in place in Europe to promote early dialogue between stakeholders on relative effectiveness assessments. In 2010, European Medicines Agency (EMA) initiated collaboration with health technology assessment (HTA) bodies through parallel scientific advice procedure and recently, EMA engaged directly HTA bodies in early access pathways to innovative medicines (adaptive pathways (AP) and Priority Medicines Scheme (PRIME)) for early dialogues during the procedures. Despite these initiatives, gap between frameworks for repurposed products and for accelerated approval is widening between regulators and payers. Discussion: Regulators introduced several procedures related to drug repurposing, such as additional exclusivity periods for well-established substances having new therapeutic indication, developed for pediatric populations or granted an orphan drug designation. Issue of value recognition for repurposed products is currently on agenda of the European Commission. On the other side, repurposed products are stigmatized by payers because of low investment risk and perceived lack of innovation, and in some countries, already existing active substances are not eligible for HTA, and subject to systematic reference pricing. Since 2005, European regulators implemented five pathways to enhance early access of innovative medicines: marketing authorization under exceptional circumstances, conditional marketing authorization, procedure for accelerated assessment, AP and PRIME; however, these medicines are facing payers’ requirements for mature data before being able to achieve expected premium prices associated to their potential added value. Conclusion: Despite multiple initiatives and efforts, gaps between regulators and payers continue to widen, impacting patient access to new/repurposed medicines: lack of payers’ rewards for repurposed medicines creates disincentives for further development; payers’ aversion to uncertainty surrounding early drug access and lack of flexible pricing to raise price when new evidence is available, lead to delayed drug launch by manufacturers to generate more mature evidence and negotiate better prices.