Research is an integral part of medical progress that leads to better understanding of disease processes and the development of therapies to improve patient care. The medical community has an obligation and societal responsibility to review its practices and advance its knowledge to optimize care for those who entrust it with their health and well-being. While ultimately intended to benefit patients specifically and society as a whole, every laboratory and clinical investigation inherently carries an element of uncertainty and has attendant risks. These can have unintended and, at times, harmful consequences that cannot justify the knowledge gained. In order to mitigate these risks and protect human subjects involved in clinical research studies, a basic framework of ethical principles has been developed to guide responsible experimental design, execution, and data dissemination. This article provides a review of these principles and the historical context from which they were derived and explores the persistent challenges and cognitive biases that can increase susceptibility to unethical research practices.