This chapter examines the evolving landscape of digitalized healthcare, with a focus on patient safety and systematic risk assessment in the context of telemedicine, artificial intelligence (AI), and e-health services. While digital solutions offer efficiency and broader access, they also introduce complexities that require robust regulatory frameworks and human-centered safeguards. Emphasis is placed on frameworks such as Safety-I and Safety-II, as well as risk management tools like Digi-HTA and the Digital Services Risk Management Tool. Legal instruments, including the GDPR, Data Governance Act, and the EU Artificial Intelligence Act, are reviewed for their role in protecting patients and guiding the ethical deployment of technology. The text emphasizes the importance of digital health competencies, equitable access, and ongoing education for both professionals and patients. Ultimately, the chapter advocates for proactive strategies, multi-stakeholder collaboration, and international standardization to ensure the development of safe, effective, and inclusive digital healthcare systems.