In this issue of the journal, Sakamoto et al. present an analysis of diffusion lesion evolution in acute ischemic stroke patients first imaged less than three-hours from stroke onset. Although temporary lesion volume reduction was observed following reperfusion, the affected regions were generally abnormal on follow-up fluid attenuated inversion recovery imaging, indicating lack of tissue salvage. Taken in conjunction with other recent articles, it seems that temporary postreperfusion ‘reversal’ of diffusion lesions is quite common but usually does not translate to permanent tissue salvage. A minority of patients demonstrate permanent reversibility of a component of the acute diffusion lesion. This is dependent on early reperfusion and is more frequent when patients are treated within three-hours. Early reperfusion is clearly associated with a reduction in infarct growth through salvage of ischemic penumbra, and this probably contributes more to the favorable neurological outcomes in these patients than the relatively small volumes of diffusion reversal. It is currently unknown whether future therapeutic advances that increase the speed and success rates of reperfusion will increase the proportion of reversibility further and lead to clinically relevant salvage within the diffusion lesion. For the present, it appears that intravenous tissue plasminogen activator rarely achieves substantial permanent reversal of diffusion lesions, even when administered within three-hours.