Basic science studies demonstrated mechanisms of plasticity and metaplasticity. More recent human studies identified some of these mechanisms as operating in multiple areas of human cognition, such as learning and memory, and in functional recovery from lesions in the CNS, as in stroke. One of the goals of neurorehabilitation is the translation of these principles into rational strategies to promote recovery of function. Understanding the mechanisms and functional role of human plasticity could lead to the development of therapeutic options in situations in which there is virtually no treatment alternative, as in chronic stroke. We review some of the work performed to better understand the substrates and mechanisms underlying cortical plasticity and discuss some experimental approaches to enhance cortical plasticity and recovery of function, like cortical stimulation.