Patient data have conventionally been thought to be well protected by the privacy laws outlined in the United States. The increasing interest of for-profit companies in acquiring the databases of large health care systems poses new challenges to the protection of patients’ privacy. It also raises ethical concerns of sharing patient data with entities that may exploit it for commercial interests and even target vulnerable populations. Recognizing that every breach in the confidentiality of large databases exposes millions of patients to the potential of being exploited is important in framing new rules for governing the sharing of patient data. Similarly, the ethical aspects of data voluntarily and altruistically provided by patients for research, which may be exploited for commercial interests due to patient data sharing between health care entities and third-party companies, need to be addressed. The rise of technologies such as artificial intelligence and the availability of personal data gleaned by data vendor companies place American patients at risk of being exploited both intentionally and inadvertently because of the sharing of their data by their health care provider institutions and third-party entities.