Neuropsychological rehabilitation involves many complex processes aimed at enabling people who are disabled by brain injury or disease to achieve their optimum level of physical, psychological, social and vocational well being. Theoretical frameworks, methodologies, and measures for evaluating the effectiveness of rehabilitative interventions and outcomes are diverse, mirroring the heterogeneity of individuals with brain injuries or disorders. This special issue draws together thinking, approaches, and methods in neuropsychological rehabilitation and their ethical implications in order to clarify many of the ideas that are currently being explored. Diverse methodologies are reviewed ranging from randomized controlled trials to cross-cultural studies to novel statistical approaches for the evaluation of small sample clinical trials and single subject investigations. Both medical model and social model research perspectives are elaborated and more specific models for conceptualizing and defining interventions are detailed. Item response theory provides a framework for creating increasingly reliable, valid, and usable rating scales to measure the process and outcomes of rehabilitation interventions. These new measurement techniques are illustrated as well as methods to include the perspective of the person whose outcome is being measured and to transadapt measures across language and culture. In reviewing current and innovative methodologies for studying neuropsychological rehabilitation in a variety of settings and from a variety of perspectives, this issue attempts to find common directions and provide guideposts through the complexities inherent in the field.