The European Health Data Space is an opportunity to promote the sharing of health data across borders. In turn, this should enable more personalized diagnoses, more innovative medical treatments, and more digital technologies to improve our health. However, any policies to share health data need to contain strong legal safeguards that not only ensure the security of the data but also ensure that the people managing these digital therapies—patients and caregivers as well as practitioners—are equipped with the appropriate skills. The already well-known Digital Competence Framework for Citizens (DigComp) has provided a common understanding across the EU and beyond of what digital competence is. One of the aims of this framework is to describe the perspectives of patients and caregivers to those involved in the R&D associated with digital health, personalized medicine, and rehabilitation therapies. This chapter therefore provides a review of the contexts in which patients are actively involved in administering healthcare. The key themes covered include: digital education, digital skills, preventing cyber and physical risk, the factors mediating digital competency, and the daily impact of digital therapies. In addition, we identify the current challenges in personalized medicine and define the needs of patients and caregivers in response. Overall, we find the “digital transformation” in health requires a cultural approach that can empower all those involved, from the patients, caregivers, and their families to practitioners and politicians. Digital skills for health are not optional; they are a necessary requirement for a conscious process of improving everyone’s quality of life. Hence, following the “All Digital Weeks” held annually in Italy, we advocate for a Digital Health Literacy Space at the national and European levels.