Critical to the clinical evaluation of effective novel therapies for lung cancer is the early and accurate determination of tumor response, which requires an understanding of the sources of uncertainty in tumor measurement and subsequent attempts to minimize their effects on the assessment of the therapeutic agent. The Reference Image Database to Evaluate Response (RIDER) project seeks to develop a consensus approach to the optimization and benchmarking of software tools for the assessment of tumor response to therapy and to provide a publicly available database of serial images acquired during lung cancer drug and radiation therapy trials. Images of phantoms and patient images acquired under situations in which tumor size or biology is known to be unchanged also will be provided. The RIDER project will create standardized methods for benchmarking software tools to reduce sources of uncertainty in vital clinical assessments such as whether a specific tumor is responding to therapy.