Recent laboratory findings suggest that it might be possible to promote cerebral plasticity and neurological recovery after stroke by use of exogenous pharmacological or cell-based treatments. Brain microvasculature and glial cells respond in concert to ischaemic stressors and treatment, creating an environment in which successful recovery can ensue. Neurons remote from and adjacent to the ischaemic lesion are enabled to sprout, and neural precursor cells that accumulate with cerebral microvessels in the perilesional tissue further stimulate brain plasticity and neurological recovery. These factors interact in a highly dynamic way, facilitating temporally and spatially orchestrated responses of brain networks. In view of the complexity of the systems involved, stroke treatments that stimulate and amplify these endogenous restorative mechanisms might also provoke unwanted side-effects. In experimental studies, adverse effects have been identified when neurorestorative treatments were administered to animals with severe associated illnesses, after thrombolysis with alteplase, and when therapies were initiated outside appropriate time windows. Balancing the opportunities and possible risks, we provide suggestions for the translation of restorative therapies from the laboratory to the clinic.