Increased prevalence of multi-drug resistance in pathogens has encouraged researchers to focus on finding novel forms of anti-infective agents. Antimicrobial peptides (AMPs) found in animal secretions are components of host innate immune response and have survived eons of pathogen evolution. Thus, they are likely to be active against pathogens and even those that are resistant to conventional drugs. Many peptides have been isolated and shown to be effective against multi-drug resistant pathogens. More than 500 AMPs have been identified from amphibians. The abundance of AMPs in frog skin is remarkable and constitutes a rich source for design of novel pharmaceutical molecules. Expression and post-translational modifications, discovery, activities and probable therapeutic application prospects of amphibian AMPs will be discussed in this article.