Stroke is a leading cause of disability in the United States and is likely to have an increasing impact on disability worldwide. In order to develop more effective rehabilitation techniques, it is critical to understand the mechanisms underlying the mature brain's capacity to reorganize and restore neurologic function. Over the past decade, functional brain imaging has been a principal investigational tool in elucidating mechanisms of stroke recovery. Functional imaging studies of motor performance in patients with stroke consistently demonstrate areas of brain activation not present in healthy subjects. The role of these additional areas in recovery after stroke remains uncertain. This review discusses methodologic and theoretical issues that impact on interpreting functional imaging studies of motor recovery after stroke.