We present two new empirical scoring functions, LigScore1 and LigScore2, that attempt to accurately predict the binding affinity between ligand molecules and their protein receptors. The LigScore functions consist of three distinct terms that describe the van der Waals interaction, the polar attraction between the ligand and protein, and the desolvation penalty attributed to the binding of the polar ligand atoms to the protein and vice versa. Utilizing a regression approach on a data set of 118 protein-ligand complexes we have obtained a linear equation, LigScore2, using these three descriptors. LigScore2 has good predictability with regard to experimental pKi values yielding a correlation coefficient, r2), of 0.75 and a standard deviation of 1.04 over the training data set, which consists of a diverse set of proteins that span more than seven protein families.