The rapid adoption of e-health applications and systems has revolutionized healthcare delivery, offering unprecedented opportunities for patient care and data management. However, this digital transformation has also introduced significant challenges in protecting sensitive patient data from unauthorized access, breaches, and misuse. This chapter provides a comprehensive analysis of the key legal regulations that govern the protection of patient data in e-health systems, focusing on the European Union (EU) and the United States (USA). We explore critical frameworks such as the General Data Protection Regulation (GDPR) and the Health Insurance Portability and Accountability Act (HIPAA), which set the standards for privacy, security, and consent in handling personal health information (PHI). The chapter also delves into real-world security breaches, highlighting incidents that have exposed vulnerabilities in e-health systems, including data breaches, ransomware attacks, and insider threats. Additionally, the chapter examines sector-specific regulations like the ePrivacy Directive, and the Twenty-first Century Cures Act, illustrating their role in safeguarding patient data in digital health ecosystems. By comparing the legal approaches and security practices across the EU and USA, this chapter underscores the critical need for robust data protection measures and highlights the challenges of ensuring patient privacy in a rapidly evolving technological landscape. The findings provide essential insights for policymakers, healthcare providers, and developers seeking to navigate the complex intersection of healthcare innovation and data security.