It is likely that 90% of all small-molecule high-performance liquid chromatography (HPLC) separations can be done with a hydrocarbon-bonded phase of C4, C8, or C18 length using various mobile phases. The remaining 10% of the cases are more challenging. One solution is to follow the historical path of gas-liquid chromatography and create more bonded phases. The second and more easily done is to add components to the mobile phase that interact selectively with the molecules of interest and change RPLC selectivity and retention. This paper begins with a generalized discussion of additive strategy and mechanism and then leads to a study of nonionic but coordinatively unsaturated (β-diketonates as additives which serves as an example of the connection between molecular chemistry and chromatographic selectivity and a review of other work done. A system of coordinatively unsaturated metal β-diketonates was investigated as mobile phase additives for HPLC. Unlike previous ionic, metal dopants, these neutral complexes combine reasonable elution times, high chromatographic efficiency, and enhanced chromatographic selectivity for polar compounds in normal and reversed-phase modes. The influences of mobile-phase composition, stationary-phase substrate, and metal on solute retention behavior were examined for the metal-dipivaloylmethane additive systems.