Research misconduct strikes at the very core of the research enterprise as a direct threat to the very integrity of research and, of course, the social policies, treatments, interventions, and future research that are based on or build on that research. The principles, policies, and processes articulated by the Office of Research Integrity (ORI), Department of Health and Human Services (DHHS), constitute the “gold standard” when it comes to dealing with research integrity. These principles are: mandated for institutions that receive DHHS funding; adopted by most institutions as the basis of their policies and procedures and generally applied to all research regardless of funding. This chapter explains what research misconduct is and is not, explores the effects of misconduct, and outlines steps to prevent, identify, and respond to this problem.