The prokaryotic and eukaryotic microorganisms that drive the pelagic ocean's biogeochemical cycles are currently facing an unprecedented set of comprehensive anthropogenic changes. Nearly every important control on marine microbial physiology is currently in flux, including seawater pH, pCO2, temperature, redox chemistry, irradiance and nutrient availability. Here, we examine how microorganisms with key roles in the ocean carbon and nitrogen cycles may respond to these changes in the Earth's largest ecosystem. Some functional groups such as nitrogen-fixing cyanobacteria and denitrifiers may be net beneficiaries of these changes, while others such as calcifiers and nitrifiers may be negatively impacted. Other groups, such as heterotrophic bacteria, may be relatively resilient to changing conditions. The challenge for marine microbiologists will be to predict how these divergent future responses of marine microorganisms to complex multiple variable interactions will be expressed through changing biogeography, community structure and adaptive evolution, and ultimately through large-scale alterations of the ocean's carbon and nutrient cycles.