The discovery that brain tissue could potentially be salvaged from ischaemia due to stroke, has led to major advances in the development of therapies for ischemic stroke. In this review, we detail the advances in the understanding of this area termed the ischaemic penumbra, from its discovery to the evolution of imaging techniques, and finally some of the treatments developed. Evolving from animal studies from the 70s and 80s and translated to clinical practice, the field of ischemic reperfusion therapy has largely been guided by an array of imaging techniques developed to positively identify the ischemic penumbra, including positron emission tomography, computed tomography and magnetic resonance imaging. More recently, numerous penumbral identification imaging studies have allowed for a better understanding of the progression of the ischaemic core at the expense of the penumbra, and identification of patients than can benefit from reperfusion therapies in the acute phase. Importantly, 40 years of critical imaging research on the ischaemic penumbra have allowed for considerable extension of the treatment time window and better patient selection for reperfusion therapy. The translation of the penumbra concept into routine clinical practice has shown that "tissue is at least as important as time."