Stings of certain ant species (Hymenoptera: Formicidae) can cause intense, long-lasting pain. Here we show that for several species this is due to a family of peptide toxins that modulate mammalian voltage-gated sodium (NaV) channels. These peptides are structurally and functionally unique among described NaV channel toxins. The complex effects of these peptides on NaV channel currents are characterised by inhibition of inactivation, a hyperpolarising shift in voltage-dependence of activation, and in some cases, a shift in reversal potential (Vrev). This peptide toxin family appears to be unique to the Formicidae where it is widespread although not ubiquitous.