More than a thousand antimicrobial peptides (AMPs) have been reported in the last decades arising from the skin secretion of amphibian species. Generally, each frog species can express its own repertoire of AMPs (typically, 10-20 peptides) with differing sequences, sizes, and spectrum of action, which implies very rapid divergence, even between closely related species. Frog skin AMPs are highly potent against antibiotic-resistant bacteria, protozoa, yeasts, and fungi by permeating and destroying their plasma membrane and/or inactivating intracellular targets. These peptides have attracted considerable interest as a therapeutic alternative to conventional anti-infective agents. However, efforts to obtain a new generation of drugs using these peptides are still challenging because of high associated R&D costs due to their large size (up to 46 residues) and cytotoxicity. This review deals with the biodiversity of frog skin AMPs and assesses the therapeutic possibilities of temporins, the shortest AMPs found in the frog skin, with 8-17 residues. Such short sequences are easily amenable to optimization of the structure and to solution-phase synthesis that offer reduced costs over solid-phase chemistry.