To make practical recommendations regarding therapeutic strategies for the rehabilitation of patients with hemiparetic stroke, it is important to have a general understanding of the fundamental mechanisms underlying the neuroplasticity that is induced by skills training and by exercise programs designed to increase muscle strength and cardiovascular fitness. Recent clinical trials have provided insights into methods that promote adaptations within the nervous system that correlate with improved walking and upper extremity function, and that can be instigated at any time after stroke onset. Data obtained to date indicate that patients who have mild to moderate levels of impairment and disability can benefit from interventions that depend on repetitive task-oriented practice at the intensity and duration necessary to reach a plateau in a reacquired skill. Studies are underway to lessen the consequences of more-severe motor deficits by drawing on medications that augment plasticity, biological interventions that promote neural repair, and strategies that employ electrical stimulation and robotics.