The U.S. EPA conducts risk assessments for an array of health effects that may result from exposure to environmental agents. These assessments often include an analysis of the dose-response relationship between exposure and health-related outcomes. The dose-response assessment is essentially a two-step process: (1) defining a point of departure (POD) and (2) extrapolating from the POD for relevance to human exposure. The benchmark dose (BMD) approach, which involves dose-response modeling to obtain BMDs, i.e., dose levels corresponding to specific response levels near the low end of the observable range of the data, incorporates and conveys more information than the No Observed Adverse Effect Level (NOAEL) or Lowest Observed Adverse Effect Level (LOAEL) process traditionally used for noncancer health effects. The approach is similar to that for determining the POD for cancer endpoints (U.S. EPA 2005a). As the Agency moves toward harmonization of approaches for cancer and noncancer risk assessment, the dichotomy between cancer and noncancer health effects is being replaced by consideration of mode of action and whether the effects of concern are likely to be linear or nonlinear at low doses. Thus, the purpose of this document is to provide guidance for the Agency and the outside community on consistent application of the BMD approach for deriving BMDs for a variety of uses, including the determination of PODs for different types of health effects data, whether a linear or nonlinear low-dose extrapolation is used. Other uses of BMDs include comparing relative potencies (e.g., across chemicals) or relative sensitivities (e.g., across different subpopulations). Note that BMD modeling is also applicable to other fields, such as ecological risk assessment; however, this document focuses on the dose-response modeling of health effects.