The United States Environmental Protection Agency (EPA) Office of Superfund Remediation and Technology Innovation (OSRTI) is responsible for implementing the long-term (non-emergency) portion of a key U.S. law regulating cleanup: the Comprehensive Environmental Response, Compensation and Liability Act, CERCLA, nicknamed “Superfund.” The purpose of the Superfund program is to protect human health and the environment over the long term from releases or potential releases of hazardous substances from abandoned or uncontrolled hazardous waste sites. This paper provides a brief overview of the approach used by EPA to conduct Superfund cleanups at contaminated sites, including those that are contaminated with radionuclides, to ensure protection of human health and the environment. The paper addresses how EPA Superfund determines if a site poses a risk to human health and the framework used to determine cleanup levels. The theme emphasized throughout the paper is that within the Superfund remediation framework, radioactive contamination is dealt with in a consistent manner as with chemical contamination, except to account for the technical differences between radionuclides and chemicals. This consistency is important since at every radioactively contaminated site being addressed under Superfund's primary program for long-term cleanup, the National Priorities List (NPL), chemical contamination is also present.