The production and deposition of melanin pigments on invading pathogens and parasites represents a unique, innate immune response in the phylum Arthropoda. This immune response has started to receive considerable attention because of the potential to exploit this mechanism to control mosquito-borne diseases. In this article, we summarize knowledge about this complex biochemistry, the use of melanin biosynthesis in diverse physiological processes and the gaps in knowledge that must be addressed if this immune process is to be manipulated in genetic-based control strategies.