The spatial neglect syndrome, defined by asymmetric attention and action not attributed to primary motor or sensory dysfunction and accompanied by functional disability, is a major cause of post-stroke morbidity. In this review, we consider the challenges and obstacles facing scientific researches wishing to evaluate the mechanisms and effectiveness of rehabilitation interventions. Spatial neglect is a heterogeneous disorder, for which consensus research definitions are not currently available, and it is unclear which of the deficits associated with the syndrome causes subsequent disability. We review current opinion about methods of assessment, suggest a rational approach to selecting therapies which requires further study, and make systems-level and theoretical recommendations for building theory. We lastly review some creative questions for consideration in future research.