The 5-HT3 receptor complex is a ligand-gated ion channel, and is therefore likely to comprise multiple subunits in common with other members of this superfamily. To date, however, only one 5-HT3 receptor subunit, plus an alternatively spliced variant, have been identified. In this article, Stephanie Fletcher and Nicholas Barnes review some of the extensive data in the literature that suggest the presence of other 5-HT3 receptor subunits. This is particularly relevant given the recent demonstration that the 5-HT3 receptor purified from pig brain contains a non-5-HT3A-like protein(s).