Stroke has become the second most prevalent cause of mortality in the world. Currently, the treatment of ischemic stroke is based on thrombolytic and thrombectomy therapy shortly after the ischemic event (≤ 4.5 h for thrombolytic strategies; ≤ 6 h for thrombectomy strategies). However, the majority of patients are unable to receive prompt treatment, particularly in undeveloped countries. Alternative solutions are lacking for those patients that miss the optimal window of opportunity for treatment. Recently, new developments in imaging techniques and intravascular interventional devices enable the expansion of the window of opportunity for treating stroke patients. Clinical studies have reported that delayed recanalization at 24 h, or even more than 1 month, was beneficial for some patients. However, the mechanisms of neuroprotection that underly the delayed recanalization in these ischemic stroke patients remain unclear. In this review, we will summarize the clinical studies of delayed recanalization, and organize them according to the duration of occlusion. Additionally, we will discuss the changing guidelines and possible mechanisms based on animal research, and attempt to draw conclusions and future perspectives.