Stroke is the second commonest cause of death and the principal cause of adult disability in the world. In most cases ischemic injuries have been reported to induce mild to severe permanent deficits. Nevertheless, recovery is often dynamic, reflecting the ability of the injured neuronal networks to adapt. Plastic phenomena occurring in the cerebral cortex and in subcortical structures after ischemic injuries have been documented at the synaptic, cellular, and network level and several findings suggest that they may play a key role during neurorehabilitation in human stroke survivors. In particular, in vitro studies have demonstrated that oxygen and glucose deprivation (in vitro ischemia) exerts long-term effects on the efficacy of synaptic transmission via the induction of a post-ischemic long-term potentiation (i-LTP). i-LTP may deeply influence the plastic reorganization of cortical representational maps occurring after cerebral ischemia, inducing a functional connection of previously non-interacting neurons. On the other hand, there is evidence that i-LTP may exert a detrimental effect in the peri-infarct area, facilitating excitotoxic processes via the sustained, long-term enhancement of glutamate mediated neurotransmission. In the present work we will review the molecular and synaptic mechanisms underlying ischemia-induced synaptic plastic changes taking into account their potential adaptive and/or detrimental effects on the neuronal network in which they occur. Thereafter, we will consider the implications of brain plastic phenomena in the post-stroke recovery phase as well as during the rehabilitative and therapeutic intervention in human subjects.