Molecular therapy requires a careful control of specificity. The authors review the recent advances in this regard focusing on a novel marker for ligand-target interaction, the solvent-exposed hydrogen bond or dehydron. Dehydrons promote their own dehydration and are not conserved across homolog proteins. Thus, the so-called wrapping technology is geared at enhancing drug specificity and hinges on an analysis of interfacial dehydrons in target-ligand complexes to assess microenvironmental changes occurring on association. Dehydron differences across purported targets have been exploited to redesign drugs in order to enhance selectivity. Tested wrapping modifications to cancer drugs are reviewed. Distance matrices defined by comparing dehydron patterns across targets correlate strongly with pharmacologic distances. This fact suggests a broad applicability of the wrapping technology, ultimately leading to molecular therapies with tighter control of side effects.