Research in neural plasticity of adult cortical representations brought hope of significant potential for further improvement in therapy after cerebrovascular stroke, but the same processes involved in plasticity also allow for maladaptive changes whether spontaneous or caused by inappropriate therapeutic manipulations. Within the extensive network of multiple and bilateral motor cortical and subcortical areas, this paper focuses on the primary motor cortex. We review selected data from humans and primates regarding its functional anatomy and the mechanisms of adaptive neuroplasticity in the presence of brain insults, and the impact of motor skill learning in normals and rehabilitation therapy in patients. The discussion centers on the potential impact of the mechanisms of motor cortex neuroplasticity, especially of the phenomenon of competition among primary motor cortical representations, on the rehabilitation of paretic hand and shoulder after stroke. Application of results from neurophysiology and functional brain imaging research into the clinical practice is in the initial stages and remains a challenge for the future. Nevertheless, even the available research provides an important message for clinical rehabilitation of stroke patients: the need to widen multimodal and interdisciplinary approaches to rehabilitation of the paretic hand.