With ongoing and rapid climate change, ecologists are being challenged to predict how individual species will change in abundance and distribution, how biotic communities will change in structure and function, and the consequences of these climate-induced changes for ecosystem functioning. It is now well documented that indirect effects of climate change on species abundances and distributions, via climatic effects on interspecific interactions, can outweigh and even reverse the direct effects of climate. However, a clear framework for incorporating species interactions into projections of biological change remains elusive. To move forward, we suggest three priorities for the research community: (1) utilize tractable study systems as case studies to illustrate possible outcomes, test processes highlighted by theory, and feed back into modeling efforts; (2) develop a robust analytical framework that allows for better cross-scale linkages; and (3) determine over what time scales and for which systems prediction of biological responses to climate change is a useful and feasible goal. We end with a list of research questions that can guide future research to help understand, and hopefully mitigate, the negative effects of climate change on biota and the ecosystem services they provide.