Increases in temperature and atmospheric CO2 concentrations directly affect plant physiology, and our predictions for how ecosystems will respond to these climate drivers is based on our understanding of these processes. But there is growing evidence that the responses of vegetation to warming and rising CO2 will be limited by other environmental factors, such as water and day length. The effects of elevated CO2 on tree fecundity are constrained by water availability, while differences in plant water use efficiency (the ratio of net photosynthesis to transpiration) underlie community composition shifts in tallgrass prairie species. Plant responses to rising temperatures also interact with water: the physiological and developmental changes induced by elevated growth temperatures can alter plant hydraulics, such that water may be a stronger control of plant mortality in a warmer world. And while warming is predicted to increase the length of the growing season and stimulate carbon uptake in northern latitudes, photoperiod constraints may limit the ability of forests to positively respond to rising temperatures. Taking a multifactorial approach to studying global change is increasingly necessary if we are to successfully predict and mitigate the effects of climate change on our natural systems.