This review looks at the efforts that are being made to modify the surface of poly(dimethylsiloxane) (PDMS) microchannels, in order to enhance applicability in the field of microfluidics. Many surface modifications of PDMS have been performed for electrophoretic separations, but new modifications are being done for emerging applications such as heterogeneous immunoassays and cell-based bioassays. These new modification techniques are powerful because they impart biospecificity to the microchannel surfaces and reduce protein adsorption. Most of these applications require the use of aqueous or polar solvents, which makes surface modification a very important topic.