The Mauna Loa carbon dioxide (CO2) time series exhibits fluctuations at periods of around 40-50 years. Landings of small pelagic populations of anchovies and sardines fluctuate at similar periods and provided early evidence for variability on these time scales. Since then signatures of this multi-decadal climate variability have been uncovered throughout the North and South Pacific. The variability is evident in the productivity of coastal and equatorial upwelling systems, the central gyre, the Gulf of Alaska and the northwestern Pacific. Productivity of the upwelling ecosystems appears out of phase with productivity in the central gyres, the Gulf of Alaska and the northwestern Pacific. During the high coastal and equatorial upwelling, anchovy regime less CO2 accumulated in the atmosphere than during the sardine regime. This is inconsistent with a stronger of flux CO2 to the atmosphere due to enhanced equatorial upwelling but consistent with an enhanced coastal and equatorial biological pump of carbon into the ocean interior. If a stronger biological pump is implicated then there must be an imbalance between carbon and other nutrients supplied by upwelling and that exported by the biological pump. A small deviation from the Redfield ratio of 6.6C:1N could account for the observed variability. Terrestrial processes may also be implicated. For example, the existence of a significant North American carbon sink, presumably resulting from changes in land use, has recently been suggested. These changes are of similar magnitude to the multi-decadal fluctuations highlighting both the capacity of terrestrial systems and the need to better understand the multi-decadal variations. New observational networks, that include key atmospheric and oceanic measurements, will be required to accurately assess natural and human influences on atmospheric CO2. Strong programs in modeling and data assimilation will need to accompany the observational networks. The North American Carbon Program, focused on the North American carbon sink, is being developed with these issues in mind and will be reviewed.