There have been exciting new discoveries over the past two decades regarding how plastic the adult brain is in response to behavioral experience, such as motor training. Increases in brain trophic factors and upregulation of protein-controlling genes, increases in synaptogenesis, and increases or alterations in motor representations are a few of the neural adaptations observed in response to motor skill training. This neural reorganization after stroke is seen as critical to enhancing upper extremity function, and many therapy protocols have preliminary evidence for their impact on neural reorganization and efficacy in facilitating improvements in motor functioning. Yet, there remain many questions regarding how to predict which particular participants with stroke will respond to the therapy, how great of a response can be expected, how intense therapy should be, and the exact nature of the best practice schedule. In this article, we briefly review the basic science literature demonstrating behavior-induced neural reorganization and then review the evidence for several of the most commonly studied motor rehabilitation interventions for humans with stroke.