In this chapter, we explore the different factors influencing fault permeability development during fracturing and sealing periods. In underground CO2 storage, the large-scale fluid pressure changes expected from industrial injections need to be kept lower, by regulation, than the intact rock fracturing pressure to avoid geomechanical damage in the reservoir and hydrofracturing in the confining caprock units. Nevertheless, these injection pressures may be high enough to activate dilatant shearing on natural pre-existing faults intersecting the reservoir-caprock system (Guglielmi et al. in Int J Greenhouse Gas Control 111, 2021). This could result in the creation of permeable flow pathways along the faults which could allow for CO2 to penetrate and migrate through the overlying sealing formations. Unless caprock clay-rich fault self-sealing occurs, the CO2 could escape from the reservoir, and eventually end up in overlying fresh-water aquifers or leak to the surface, thus creating a risk to the environment and defeating the sequestration purpose. In Sects. 3.1, 3.2, 3.3 and 3.4, we review different factors influencing single-fractures permeability evolution under shear, reporting observations at laboratory scale. In Sect. 3.5, we explore how permeability of a fault zone can vary under activation at field scale. This chapter summarizes the key results from several field scale fault activation experiments. In these experiments, fluid pressure was increased through fluid injections conducted directly into natural fault zones affecting a wide variety of rock geology. In Sect. 3.6, we suggest a conceptual model of a fault zone permeability evolution with fault plastic rupture, and we report on some permeability laws that could help to consider such evolution in advanced numerical models.