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The first research on the insect <i>Galleria mellonella</i> was published 85 years ago, and the larva is now widely used as a model to study infections caused by bacterial and fungal pathogens, for screening new antimicrobials, to study the adjacent immune response in co-infections or in host-pathogen interaction, as well as in a toxicity model. The immune system of the <i>G. mellonella</i> model shows remarkable similarities with mammals. Furthermore, results from <i>G. mellonella</i> correlate positively with mammalian models and with other invertebrate models. Unlike other invertebrate models, <i>G. mellonella</i> can withstand temperatures of 37 °C, and its handling and experimental procedures are simpler. Despite having some disadvantages, <i>G. mellonella</i> is a virtuous in vivo model to be used in preclinical studies, as an intermediate model between in vitro and mammalian in vivo studies, and is a great example on how to apply the bioethics principle of the 3Rs (Replacement, Reduction, and Refinement) in animal experimentation. This review aims to discuss the progress of the <i>G. mellonella</i> model, highlighting the key aspects of its use, including experimental design considerations and the necessity to standardize them. A different score in the “cocoon” category included in the <i>G. mellonella</i> Health Index Scoring System is also proposed.