Human health and well-being are central to EU policies and programs. In the field of social rights, these programs aim at a fairer, more inclusive and more social Europe for all European citizens, based on the European social model for the challenges of the 21st century. Providing timely access to good quality healthcare for all citizens is one of the EU's key objectives. This is in line with the UN's goal of sustainable development, which calls for universal health care for all citizens by 2030, so that preventable deaths could be eradicated. The main challenge is to work on persistent health inequalities between and within EU countries. Furthermore, the need to respond to the increase in certain types of diseases, such as oncological diseases, non-communicable diseases or mental illnesses and, last but not least, infectious diseases. Improving the promotion of disease prevention, including vaccination, will also be a challenge. Other areas that need to be addressed are: the impact of increasing environmental pollution on human health, growing resistance to antimicrobials, demographic change, even in the context of an aging population. Research and innovation to be supported in Cluster 1 should aim at advancing knowledge, building capacity, developing innovative solutions that will improve people's health and well-being and support the transformation of healthcare systems.