The interaction of a drug molecule with biomolecules is affected by the enormous abundance of nonspecific targets in a living organism, with the estimated ratio to a specific receptor being 107 to 1. This chapter discusses the difference between complexes with a nonspecific acceptor and with a specific acceptor. The thermodynamic minimum might not be reached within the time of interaction in the former case as a result of kinetic factors. The role of long-range and close contact electrostatic interactions in drug recognition is also described. The molecular electrostatic potential (MEP) makes it possible to classify receptors into various types interacting with ligands remotely and selecting specific ligands through MEP similarity. To avoid nonspecific absorption, an ideal drug molecule should have precise correspondence of its MEP to the receptor’s one. Different groups in a ligand molecule (charged, dipole polar, nonpolar aromatic, and aliphatic) interact in a stepwise manner. When approaching the acceptor, a molecule can recognize it on a long-range distance. Trials and errors make this process competitive and selective.