In this contribution the hydration kinetics of three anhydrous poly-morphs (AH-A, AH-B and AH-C) of fluconazole [2-(2,4-diﬂuorophenyl)-1,3-bis (1H- 1,2,4-triazol-1-yl)-propan-2-ol] were studied. The conversion kinetics from the anhydrous forms to the monohydrate (MH) were monitored at various relative humidities above the critical water activity. The studies revealed very different kinetic stabilities for the three anhydrous forms, with AH-A and AH-C converting much more easily to the MH than AH-B. Various energetic factors, which may be influencing the kinetics of hydration, were explored together with crystal structure and molecular conformation similarities between the anhydrous forms and the MH. The level of conformational and packing similarity between the anhydrous and MH structures was found to be consistent with the ease of hydration. We believe that surface similarity may be required for the nucleation of the hydrate, whilst the level of crystal packing similarity impacts the ease of growth. In terms of conformational variations, AH-B was found to require a significantly more dramatic conformational change to convert to the MH con-formation than those in either AH-A or AH-C. Soft planes (low attachment energies) may allow for easier diffusion of solvent into the crystal structure to allow for solvation. The overall kinetic energy barrier of water diffusion into the lattice plus conformational change was found to correlate well with our observed hydration kinetics, indicating that both the crystal structure and the conformation play a role in the kinetic stability towards hydration of the various fluconazole polymorphs.