Objectives: Advanced therapy medicinal products (ATMPs) are a new class of therapeutic interventions, based on gene, cell and tissue manipulations, offering potentially curative treatment options for a range of diseases. While the ATMP classification system is solely a European phenomenon, gene and cell-based therapies (ATMP‑like therapies) are emerging across markets and so the question of how these innovative, yet costly, treatments are to be reimbursed is pertinent worldwide. The aim of our research is to: review the current situation surrounding ATMP HTA and reimbursement in Europe, Canada and the US; identify specific challenges to ATMP market access; ascertain if and how assessment procedures are likely to change over the next 3 years. Methods: Targeted literatures searches and payer interviews (n=10) were carried out focussing on ATMPs and ATMP-like therapies awarded centralised marketing authorisation by the EMA, FDA or CADTH. Results: The national systems for HTA and reimbursement of ATMPs, like those for conventional drugs, vary country-by-country. While regulatory agencies have ATMP, or gene- and cell-therapy specific policies, HTA and reimbursement bodies do not; hence in many cases, the assessment of ATMPs for reimbursement is largely in line with that for conventional therapies. For ATMPs offering long-term curative effects, the majority of payers identified uncertainty over long-term efficacy as the greatest challenge to optimal reimbursement. Payers discussed, among others, pay-for-performance contracts, rebate contracts, and real-world evidence collection as strategies that can be utilised by manufacturers to mitigate the uncertainty and high costs associated with ATMPs. Conclusion: The high cost of ATMPs coupled with the uncertainty of long-term efficacy is the greatest challenge to ATMPs gaining market access. Overall, the key concern for payers is how to mitigate the risks of reimbursing a treatment with uncertain long‑term outcomes.