Bioaminergic receptors are involved in controlling a variety of physiological functions. An approach to predict the functional sites in bioaminergic receptors was described and applied in this study. Given an alignment and receptors with already known subfamily definition, the method identified the global and subfamily-specific functional sites based on the position-specific conservation score in both family and subfamily. Global functional sites which highly conserved in the bioaminergic receptors are play important roles in structure and responsible for the common mechanisms of receptor activation and G protein coupling. Subfamily-specific functional sites are conserved in one subfamily but vary between other subfamilies. They are mainly involved in ligand binding and G protein coupling. As research about these subfamily-specific sites is rather limited, our prediction data have an important meaning for further elucidating the specific functions of subfamily in bioaminergic receptors.