Healthcare data is an ever-growing treasure trove of information requiring complex, technological solutions for its storage, safeguarding, and accessibility. As the information is fundamentally about individuals, it must be safeguarded to ensure privacy and confidentiality of the patient. At the same time, it must be accessible and useful for patient care and enterprise-wide investigations to inform clinical health decisions at a population level. This chapter seeks to develop the digital health literacy of readers to be better informed regarding the organization of health care’s data enterprise as it develops in the age of Big Data, the Internet of Medical Things (IoMT), and Healthcare 4.0. To begin, U.S. Privacy and Security Legislation governing healthcare data will be summarized. Using the 4 layers of IoMT infrastructure, the electronic health record will be discussed to highlight enterprise solutions to safeguard healthcare data. Due to the importance of human factors in this endeavor and that safety breaches result most often from human error, the role of healthcare professionals and the patient will also be summarized. Finally, specific clinical applications including DNA data will be discussed to illustrate the constructs developed.