Improving access to medicines is a major healthcare challenge for low-income countries because the problem traverses health systems, society and multiple stakeholders. The Annapurna region of Nepal provides a valuable case study to investigate the interplay between medicines, society and health systems and their effects on access to and use of medicines. Government health facilities and international aid organizations provide some healthcare in the region, communities participate actively in healthcare organization and delivery, there is an important tourism sector and a mostly rural society.This study investigates access to and use of medicines through health facility and household-based studies using standardised tools and through a series of structured key informant interviews with various stakeholders in health.Overall, access to essential medicines at public health facilities was good, but this was not benefitting households as much as it should. People were using the private sector for medicines because of their perception about the quality and limited numbers of government-supplied free medicines. They utilised money from remittances and tourism, and subsidised healthcare from non-government organizations (NGOs) to access healthcare and medicines. A pluralistic healthcare system existed in the villages. Inappropriate use of medicines was found in households and was linked to the inadequate health system, socioeconomic and sociocultural practices and beliefs. Nevertheless, the often disadvantaged Dalit users said that they did not face any discrimination in access to health services and medicines. The government as the main stakeholder of health was unable to meet people’s health services and medicines needs; however, health aid agencies and the local community supported these needs to some extent.This study shows that the interconnectedness between medicines, society and health systems impacts the way people access and use medicines. Improving access to medicines requires an improvement in public’s perception about quality, actual coverage and appropriate use of medicines and health services via collaborative contributions of all stakeholders.