Quantitative autoradiographic methods for in vivo measurement of regional rates of cerebral blood flow, glucose metabolism, and protein synthesis contribute significantly to our understanding of phsysiological and biochemical responses of the brain to changes in the environment. A disadvantage of these autoradiographic methods is that experimental animals can be studied only once. With the advent of small animal positron emission tomography (PET) and with increases in the sensitivity and spatial resolution of scanners it is now possible to use adaptations of these methods in experimental animals with PET. These developments allow repeated studies of the same animal, including studies of the same animal under different conditions, and longitudinal studies. In this review we summarize the tradeoffs between the use of autoradiography and small animal PET for functional brain imaging studies in animal research.