Scorpion beta-toxins (beta-ScTxs) modify the activity of voltage-gated sodium (Na_v) channels, thereby producing neurotoxic effects in diverse organisms. For this reason, beta-ScTxs are essential tools not only for discriminating among different channel sub-types but also for studying the mechanisms of channel gating and the structure-function relationship involved in this process. This review considers both the structural and the functional implications of the beta-ScTxs after they bind to their receptor sites, in accord with their classification into a) anti-mammalian beta-ScTxs, b) anti-insect selective excitatory beta-ScTxs, c) anti-insect selective depressant beta-ScTxs and d) beta-ScTxs active on both insect and mammals Na_v channels. Additionally, the molecular mechanism of toxin action by the “voltage sensor trapping” model is discussed, and the systemic effects produced by these toxins are reviewed.