Impetigo (school sores) is a common superficial bacterial skin infection affecting around 162 million children worldwide, with the highest burden in Australian Aboriginal children. While impetigo itself is treatable, if left untreated, it can lead to life-threatening conditions, such as chronic heart and kidney diseases. Topical antibiotics are often considered the treatment of choice for impetigo, but the clinical efficacy of these treatments is declining at an alarming rate due to the rapid emergence and spread of resistant bacteria. In remote settings in Australia, topical antibiotics are no longer used for impetigo due to the troubling rise of antimicrobial resistance, demanding the use of oral and injectable antibiotic therapies. However, widespread use of these agents not only contributes to existing resistance, but also associated with adverse consequences for individuals and communities. These underscore the urgent need to reinvigorate the antibiotic discovery and alternative impetigo therapies in these settings. This review discusses the current impetigo treatment challenges in endemic settings in Australia and explores potential alternative antimicrobial therapies. The goals are to promote intensified research programs to facilitate effective use of currently available treatments, as well as developing new alternatives for impetigo.