A general pharmacophore model of P-glycoprotein (P-gp) drugs is proposed that is based on a highly diverse data set and relates to the verapamil binding site of the protein. It is derived from structurally different drugs using the program GASP. The pharmacophore model consists of two hydrophobic points, three hydrogen bond (HB) acceptor points, and one HB donor point. Pharmacophore patterns of various drugs are obtained, and different binding modes are presumed for some of them. It is concluded that the binding affinity of the drugs depends on the number of the pharmacophore points simultaneously involved in the interaction with P-gp. On the basis of the obtained results, a hypothesis is proposed to explain the broad structural variety of the P-gp substrates and inhibitors: (i) the verapamil binding site of P-gp has several points that can participate in hydrophobic and HB interactions; (ii) different drugs can interact with different receptor points in different binding modes.