Preclinical studies have established that anesthesia is toxic to the brain in neonatal animals, but scant research investigates the neurodevelopmental effects of exposure to anesthesia. In this article, we discuss the issue of outcome measurement of children after anesthesia administered between infancy and approximately 4 years of age. Recent studies are reviewed with the goal of understanding the contributions and limitations of the extant literature with respect to neurodevelopmental outcome. A review of school-based information (academic achievement and learning disability characterization), which are most frequently applied to measure cognitive outcome in cohort studies, is provided. The strengths and limitations of this literature is reviewed, followed by a discussion of how future trials investigating neurodevelopmental outcome after anesthesia might be improved by procedures designed specifically to assess the status of the central nervous system. Neuropsychological assessment is described and proposed as a way to increase the validity and sensitivity of forthcoming studies that intend to evaluate the short- and long-term effects of exposure to anesthesia during infancy and early childhood.