Human subjects research is systematic, scientific investigation that can be either interventional (a "trial") or observational (no "test article") and involves human beings as research subjects, commonly known as test subjects. Human subjects research can be either medical (clinical) research or non-medical (e.g., social science) research. Systematic investigation incorporates both the collection and analysis of data in order to answer a specific question. Medical human subjects research often involves analysis of biological specimens, epidemiological and behavioral studies and medical chart review studies. (A specific, and especially heavily regulated, type of medical human subjects research is the "clinical trial", in which drugs, vaccines and medical devices are evaluated.) On the other hand, human subjects research in the social sciences often involves surveys which consist of questions to a particular group of people. Survey methodology includes questionnaires, interviews, and focus groups.

Human subjects research is used in various fields, including research into advanced biology, clinical medicine, nursing, psychology, sociology, political science, and anthropology. As research has become formalized, the academic community has developed formal definitions of "human subjects research", largely in response to abuses of human subjects.

The United States Department of Health and Human Services (HHS) defines a human research subject as a living individual about whom a research investigator (whether a professional or a student) obtains data through 1) intervention or interaction with the individual, or 2) identifiable private information (32 CFR 219.102). (Lim, 1990)

As defined by HHS regulations (45 CFR 46.102):

In 2010, the National Institute of Justice in the United States published recommended rights of human subjects:

The term research subject has traditionally been the preferred term in professional guidelines and academic literature to describe a patient or an individual taking part in biomedical research. In recent years, however, there has been a steady shift away from the use of the term 'research subject' in favour of 'research participant' when referring to individuals who take part by providing data to various kinds of biomedical and epidemiological research.

In general, it can be said that experimental infections in humans are tightly linked to a history of scandals in medical research, with scandals being followed by stricter regulatory rules. Ethical guidelines that govern the use of human subjects in research are a fairly new construct. In 1906 some regulations were put in place in the United States to protect subjects from abuses. After the passage of the Pure Food and Drug Act in 1906, regulatory bodies such as the Food and Drug Administration (FDA) and institutional review boards (IRBs) were gradually introduced. The policies that these institutions implemented served to minimize harm to the participant's mental or physical well-being.^{[citation needed]}

The Common Rule, first published in 1991, also known as the Federal Policy for the Protection of Human Subjects, is dictated by the Office of Human Research Protections under the United States Department of Health and Human Services and serves as a set of guidelines for institutional review boards (IRBs), obtaining informed consent, and Assurances of Compliance for human subject participants in research studies. On January 19, 2017, a final rule was added to the Federal Register with an official effective date of July 19, 2018.