Adaptation is one of physiology's fundamental tenets, operating not only at the level of species, as Darwin proposed, but also at the level of tissues, cells, molecules and, perhaps, genes. During recent years, stroke neurobiologists have advanced a considerable body of evidence supporting the hypothesis that, with experimental coaxing, the mammalian brain can adapt to injurious insults such as cerebral ischaemia to promote cell survival in the face of subsequent injury. Establishing this protective phenotype in response to stress depends on a coordinated response at the genomic, molecular, cellular and tissue levels. Here, I summarize our current understanding of how 'preconditioning' stimuli trigger a cerebroprotective state known as cerebral 'ischaemic tolerance'.