The first generation of porous polymer monoliths emerged in the early 1990s. Their well known advantages included ease of the preparation, robustness, high permeability to flow, and mass transfer via convection. These features made them useful for the chromatographic separation of large molecules and as supports for immobilized enzymes. However, these monoliths lacked mesopores, and therefore, exhibited only a small surface area. This then prohibited the polymer-based monolith from use for the highly efficient separations of small molecules.  To avoid this weakness, we have developed and demonstrated the second generation monoliths prepared using hypercrosslinking of poly(chloromethylstyrene-co-styrene-co-divinylbenzene) polymers and obtained materials with a surface area as large as 600 m²/g that enabled the desired separation of small molecules. We also used two approaches to modulate the chemistry of these porous monolithic polymers: (i) chemical reactions of the hypercrosslinked polymers and (ii) hypercrosslinking of copolymers containing functional styrene derivatives such as 4-acetoxystyrene and 4-methylstyrene. Recently, we used “plain” poly(styrene-divinylbenzene) monoliths and hypercrosslinked them with external crosslinkers including 4,4′-bis(chloromethyl)-1,1′-biphenyl, 1,4-bis(chloro-methyl)benzene, and dimethoxymethane. Polymers with extremely large surface areas reaching up to 900 m²/g were obtained via hypercrosslinking precursor monolith polymerized for only 2.5 h. The increase in chromatographic performance of monoliths modified using this new procedure was comparable to the performance obtained with earlier monolithic polymers containing chloromethylstyrene. However, the preparation of the binary copolymer poly(styrene-divinylbenzene) precursor is simpler than that of the ternary copolymer containing chloromethylstyrene.