Technical Abstract: The cross-site comparisons presented in the previous chapters are all conducted after the individual studies are completed. The differences in experimental design in individual studies in a posteriori cross-site studies limit the scope of questions that can be addressed, and the powerfulness and confidence in the conclusions. This chapter describes cross-site studies that are “by design” where the questions, experimental layout, methods, and measurements included multiple sites from the beginning. These a priori cross-site studies provide powerful tools to understand the phenomenon of global change and to predict its impacts on ecosystems and society. Two types of a priori cross-site studies are described: (1) experimental manipulations of drivers or system properties, and (2) observations or monitoring of natural or managed ecosystems located along environmental gradients. Within each type, examples of both on-going or completed experiments and new or developing experiments are presented. For each example, insights that would not have been obtained with other approaches are also presented. The limitations and difficulties of this type of studies are listed.