Essential medicines save lives and improve health when they are available, affordable, of assured quality and properly used. Lack of access to essential medicines is one of the most serious global public health problems and many new medicines are becoming expensive even for the health systems of high- and middle-income countries. This policy brief focuses on the issues and challenges in access to medicines faced by the 11 countries of the WHO Regional Office for Europe Small Countries Initiative. Many of these countries’ challenges arise from or are aggravated because of the size of their pharmaceutical markets. Small countries have low negotiating power and country-specific requirements such as producing tailored health technology assessment (‎HTA)‎ and pricing and reimbursement dossiers, packaging and leaflets in local languages also decreases the appeal for marketing products in small countries. Furthermore, development of HTA, managed entry agreements and horizon scanning processes requires resources and specialized knowledge and skills often less available in small countries, leading to less favourable procurement terms for public payers. The strategy to address these issues and challenges is through voluntary cooperation, on joint horizon scanning, pooled demand and procurement, and HTA integration, which the Access to Novel Medicines Platform can support.