The National Institute of Clinical Excellence (NICE) was established in the United Kingdom in April 1999 to issue guidance for the National Health Service (NHS) on the use of selective new health care interventions. This article describes the NICE requirements for both incidence-based cost-effectiveness analyses and prevalence-based estimates of the aggregate NHS impact of the new drug. The article demonstrates how both of these requirements can be met using Markov modeling techniques. A Markov model for a hypothetical new treatment for HIV infection is used as an illustration of how to generate the estimates that are required by NICE. The article concludes with a discussion of the difficulties of obtaining data of sufficient quality to include in the Markov model to ensure that the submission meets all the NICE requirements and is credible to the NICE advisory board.