We present an all-atom, fixed-charge force field for amino acids with fluorinated alkyl side chains that is compatible with the AM-BER force field for proteins. With it we investigate how mono-, di-and trifluorination alters amino acid solvation. Our predictions indicate that side chain fluorination alters the hydration free energy of amino acids in surprising ways: DDG Hyd strongly depends on the chirality and location of the fluorinated site and on the identity of the amino acid. Using a simple, analytical solvation model (Equation ), we trace back these dependencies to the multiple mechanisms by which fluorination alters solvation of amino acids: there is a cost of introducing larger fluorine atoms, gains and costs associated with the higher polarity of fluorinated alkyl groups, and gains or costs from altering the number of backbone-water hydrogen bonds as a result of changed conformational preferences. For small molecules, it is often possible to predict the sign and even estimate the magnitude of the change in hydrophobicity upon fluorination. In contrast, for complex molecules 'the devil is in the details': the contribution of each mechanism to the overall hydrophobicity depends on conformational preferences and interactions between different parts of the molecule, making rules-of-thumb insufficient. For example, monofluorination does not always make amino acids more hydrophilic; similar increases in the solvent-exposed surface area of different molecules do not imply that the molecules will experience similar increases in hydrophobicity. Solvent accessible surface area descriptors of hydration free energies remain useful for complex molecules, but only when other contributions are properly accounted for.