PURPOSE OF REVIEW: Studies in humans and animal models show that most recovery from impairment occurs in the first 1-3 months after stroke as a result of both spontaneous recovery as well as increased responsiveness to enriched environments and training. Improvement from impairment is attributable to a short-lived "sensitive period" of post-stroke plasticity defined by unique genetic, physiological, and structural events. Unfortunately, rehabilitative interventions in humans have not been able to exploit this sensitive period similar to that seen in animal models. Here, we review these data and suggest a path forward. RECENT FINDINGS: Pre-clinical data reveal underlying mechanisms that define the post-stroke sensitive period. These data are then discussed in the context of the spontaneous post-stroke recovery described in humans. Future work will need to capitalize on unique interactions between the sensitive period, spontaneous recovery, and novel types of rehabilitative interventions.