Forest trees are exposed to a myriad of single and combined stresses with varying strength and duration throughout their lifetime, and many of the simultaneous and successive stress factors strongly interact. While much progress has been achieved in understanding the effects of single stresses on tree performance, multiple interacting stress effects cannot be adequately assessed from combination of single factor analyses. In particular, global change brings about novel combinations of severity and timing of different stresses, the effects of which on tree performance are currently hard to predict. Furthermore, the combinations of stresses commonly sustained by trees change during tree ontogeny. In addition, tree photosynthesis and growth rates decline with increasing tree age and size, while support biomass in roots, stem and branches accumulates and the concentrations of non-structural carbohydrates increase, collectively resulting in an enhancement of non-structural carbon pools. In this review, tree physiological responses to key environmental stress factors and their combinations are analyzed from seedlings to mature trees. The key conclusions of this analysis are that combined stresses can influence survival of large trees even more than chronic exposure to a single predictable stress such as drought. In addition, tree tolerance to many environmental stresses increases throughout the ontogeny as the result of accumulation of non-structural carbon pools, implying major change in sensing, response and acclimation to single and multiple stresses in trees of different size and age.