One longstanding theme in Dan Yakir’s research compendium has been assessment of change in isotope composition as an indicator of tree and forest performance according to complex interactions between physiology and environment. Analysis of leaf gas exchange and leaf isotope composition is one way to accomplish this assessment, but tree rings offer the potential for evaluating ecophysiology-environment relationships much farther back in time. Furthermore, temporal insights from tree rings can be gleaned at sub-annual to century scales, and even large spatial perspectives are possible with networks of sampling sites. Application of tree-ring isotopes to ecological and climate studies has grown tremendously in the last 20 years, informing a sweeping array of investigations ranging from local environmental influences to teleconnections with large-scale climate modes. This presentation highlights findings of selected studies in the US Southwest and in China, illustrating utility of tree-ring isotopes to improve understanding of ecophysiology-environment interactions at the tree and site level and to infer large-scale climate variability.