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A number of negative emission technologies (NETs) have been proposed to actively remove CO2 from the atmosphere, with enhanced silicate weathering (ESW) as a relatively new NET with considerable climate change mitigation potential. Models calibrated to ESW rates in lab experiments estimate the global potential for inorganic carbon sequestration by ESW at about 0.5-5 Gt CO2 year−1, suggesting ESW could be an important component of the future NETs mix. In real soils, however, weathering rates may differ strongly from lab conditions. Research on natural weathering has shown that biota such as plants, microbes, and macro-invertebrates can strongly affect weathering rates, but biotic effects were excluded from most ESW lab assessments. Moreover, ESW may alter soil organic carbon sequestration and greenhouse gas emissions by influencing physicochemical and biological processes, which holds the potential to perpetuate even larger negative emissions. Here, we argue that it is likely that the climate change mitigation effect of ESW will be governed by biological processes, emphasizing the need to put these processes on the agenda of this emerging research field.