Because of their mineralogy, active clays are very sensitive to changes in the type and concentration of species dissolved in the pore water. At a molecular level, this sensitivity can be explained by variations in the short range interaction forces acting between clay platelets immersed in the pore water. While models based on equilibrium of short range interaction forces can be used to predict the volumetric behavior of dilute clay suspensions, different approaches must be invoked for real soils. Natural and compacted soils react differently from dilute suspensions to chemical changes because of their fabric. It is therefore not possible to derive reliable relationships (at least from the quantitative point of view) describing the chemo-mechanical behavior of active soils solely on basis of mineralogical and chemical properties. Both microscopic experimental evidences and modeling approaches are here used to analyze the effects imparted by fabric on the coupled hydro-chemo-mechanical behavior of an active clay soil.