The role of polymer side chains in conferring selectivity to a sensing organic thin-film transistor is investigated. Alkyl- and alkoxy-substituted regioregular polythiophenes are used as active layers, and a set of volatile organic compounds carrying different chemical functionalities are employed as analytes. The responses of both polymer-based transistor and quartz crystal microbalance sensors are evaluated and compared; the sensing mechanisms involving weak interactions between the analyte functionalities and the polymers' side chains are discussed as well.