The rodent is a particularly valuable model with which to test therapeutic interventions for aging, as rodent physiology is close enough to human physiology to give the findings relevance for human aging, and it is small enough to allow for use of statistically robust sample sizes. There are many rodent models to choose from, with advantages and disadvantages to each. The choice of model system, as well as other experimental design decisions such as diet and housing, is extremely important for the success of lifespan studies. These issues are discussed in this review of the use of the rodent model. The National Institute on Aging (NIA) Interventions Testing Program, which has grappled with all of these issues, is described.