The venoms of arthropod predators such as spiders, scorpions and centipedes are dominated by disulfide-rich peptides that evolved to target a wide variety of ion channels and receptors in the nervous system of prey and predators. We have used both low- and high-throughput approaches to screen these natural combinatorial peptide libraries for peptides that target ion channels involved in human disease. I will show examples of spider-venom peptides with different modes of action that are providing leads for the treatment of epilepsy and stroke. I will describe the discovery and biophysical characterization of these peptides, including their three-dimensional structure, mode of channel binding, and mechanism of action. Moreover, I will demonstrate the therapeutic effects of these peptides in relevant animal disease models.