The vertical separation of organic matter formation from respiration can lead to net carbon sequestration within the ocean's interior, making the biological pump an important component of the global carbon cycle. Understanding the response of the biological pump to the changing environment is a prerequisite to predicting future atmospheric carbon dioxide concentrations. Will the biological pump weaken or strengthen? Currently the ocean science community is unable to confidently answer this question. Carbon flux at approximately 1000 m depth, the sequestration flux, determines the removal of carbon from the atmosphere on time scales ≥100 yr. The sequestration flux depends upon: (1) input rates of nutrients allochthonous to the ocean, (2) the export flux at the base of the euphotic zone, (3) the deviation of carbon fixation and remineralization from Redfield stoichiometry, and (4) the flux attenuation in the upper 1000 m. The biological response to increasing temperature, ocean stratification, nutrient availability and ocean acidification is frequently taxa-and ecosystem-specific and the results of synergistic effects are challenging to predict. Consequently, the use of global averages and steady state assumptions (e.g. Redfield stoichiometry, mesopelagic nutrient inventory) for predictive models is often insufficient. Our ability to predict sequestration flux additionally suffers from a lack of understanding of mesopelagic food web functioning and flux attenuation. However, regional specific investigations show great promise, suggesting that in the near future predictions of changes to the biological pump will have to be regionally and ecosystem specific, with the ultimate goal of integrating to global scales.