Over the past 65 million years (the Cenozoic) Earth's climate has drifted between warmer and cooler states via sustained, multi-million year secular trends. Superimposed on these trends are numerous more abrupt (<10^6 year) shifts and transient perturbations. Spatial and temporal patterns in isotopic paleo-proxy data, in combination with other traditional biological and sedimentological evidence, provide evidence linking many of these short- and long-term changes to global alteration of the carbon and water cycles. I will offer a set of examples on timescales ranging from thousands to millions of years, highlight anomalous features of these events that challenge standing biogeochemical theory, and discuss ongoing and new efforts to develop and test synthetic theories for the coupling of climate, hydroclimatology, and the global carbon cycle throughout the Cenozoic.