Environment polarity can cause changes in absorbance or emission maxima, for a given fluorophore. This is termed solvatochromism. In this study semiempirical models of solvatochromic shifts are used to predict their lipid bilayer location. Four reaction field models are analyzed and compared, to provide the most accurate prediction of fluorophore solvatochromic shifts using a modified version of the Lippert equation. For curcumin, the reaction field of Block and Walker gave the strongest agreement between experimental and predicted values (r = 0.978, p < 0.0001). For aluminum phthalocyanine disulfonic acid (AlPcS2), the reaction field of Wertheim, based on statistical mechanics, gave the best agreement (r = 0.951, p = 0.001) only when dispersion forces and solute polarizability are considered. The results of these models are correlated to the Dimroth-Reichardt ET(30) solvent polarity scale used by Frimer and colleagues. Using the model predicted values, curcumin is estimated to be 1-1.2 nm from the phospholipid-water interface, in the acyl chain region of the lipid bilayer. AlPcS2 is predicted to be 0.7-0.9 nm from the interface, at the fatty acid carbonyl. This investigation provides semiempirical methods to efficiently link fluorophore solvatochromic shifts to a location in the lipid bilayer via reaction field models.