The Pacific Ocean has played a major role in climate evolution throughout the Cenozoic (65–0 Ma). It is a fundamental component of global heat transport and circulation, the dominant locus of primary productivity, and, consequently, the largest reservoir for carbon exchange between the oceans and the atmosphere. A satisfactory understanding of the Cenozoic evolutionary history of the Pacific and its impact on global climate is currently data-limited. Nevertheless, the large dynamic range of Cenozoic conditions sets the stage to greatly expand our understanding of global climate and biogeochemical cycles. Past Earth “experiments” are particularly useful to understand interactions between climate and geosystems under different greenhouse gas loads. We highlight in this review four important problems in which the Pacific played a major role: the effect of changing geographic boundary conditions on ocean circulation; interactions between the carbon cycle and climate; the Pacific Ocean's influence on North American climate and its water cycle; and the gradual evolution of climate systems.