Fermentation processes offer a promising alternative for the production of chemicals by more environmentally benign routes. However, a major challenge in applying this technology remains the recovery of typically highly hydrophilic products from the complex broth. Here, we report the results of a study with the aim to enhance the separation of organic acids from fermentation broths by liquid-liquid extraction by improved design of the extractant. Based on extensive literature research supported by molecular modeling and isothermal titration calorimetry (ITC) experiments, different groups of extractants were evaluated, including amines, amides, superbases, guanidines and N-oxides. Octanol, 2-octyl-1-dodecanol and heptane were used as solvents. After extraction, a sample of the aqueous phase was analyzed with high performance liquid chromatography (HPLC) and the distribution coefficients were calculated. The obtained results showed that tertiary amines remain the state-of-the-art extractants for the recovery of organic acids. Highly basic compounds, like guanidines or superbases, as well as the N-oxides, were not able to outperform the tertiary amines. The performed work demonstrated that the applied molecular modeling tools were not sufficient to adequately assess the interactions observed between amines and organic acids.