A simple and economic method is presented that allows the preparation of transparent polystyrene (PS) substrates activated with chlorosulfonyl groups. Chlorosulfonation has been analyzed by ATR-FTIR. Linear PS chains with different degrees of chlorosulfonation have been synthesized as model compounds in order to analyze the modification quantitatively. After chlorosulfonation the activated surfaces can be quantitatively converted in aqueous solution at room temperature to sulfo or sulfonazide groups or react with bifunctional aliphatic amines of different length via formation of sulfonamide linkages. In this way, surfaces with a huge variety of functionalities like amines, carboxylic or sulfonic groups, sulfonazides, esters, etc. may be obtained in a selective way controlling their density at the surface. In all cases, functional surfaces with excellent optical transparency are obtained. Aminated surfaces have successfully been probed for ELISA assays.