Preceding sessions have focused on a specific stressor or environment, the adaptation to which can potentially be utilised to reduce strain or improve tolerance when exposed to a novel stressor. This is termed cross adaptation, while the underlying molecular basis providing cellular protection is termed cross tolerance. Cross adaptation and tolerance have great promise in occupational (esp. military), recreational, health and clinical settings, for mechanistic and practical reasons. Applying animal-based data of cross adaptation and cross tolerance to practical settings for humans at the extremes has, however, been underwhelming, e.g., for well-trained athletes using hypoxic, heat or nutritional stressors to enhance fitness per se, or patients using remote ischaemic conditioning before surgery. This presentation will therefore address the integrative context to cross adaptation and tolerance, focusing on combined-stressor contexts. Special consideration is given to exercise because it is a uniquely valuable stimulus for several reasons; (a) it contains at least six separate and self-regulating stressors, imposed endogenously, (b) it is almost universally accessible and highly dosable in time, space and intensity, and (c) cross adaptation is mediated by improved control of multiple homeostatically-regulated variables and thereby confers cross adaptation against myriad acute and life-long stressors.