Melanins are a class of pigments that are ubiquitous throughout biology. They play incredibly diverse and important roles ranging from radiation protection to immune defense, camouflage, and virulence. Fungi have evolved to use melanin to be able to persist in the environment and within organisms. Fungal melanins are often located within the cell well and are able to neutralize reactive oxygen species and other radicals, defend against UV radiation, bind and sequester non-specific peptides and compounds, and produce a physical barrier that defends the cell. For this reason, melanized fungi are often well-suited to be human pathogens—melanin allows fungi to neutralize the microbicidal oxidative bursts of our innate immune system, bind and inactivate to antimicrobial peptides and enzymes, sequester antifungal pharmaceuticals, and create a shield to block immune recognition of the fungus. Due to the importance and pervasiveness of melanin in fungal virulence, mammalian immune systems have evolved antifungal strategies that involve directly detecting and binding to fungal melanins. Such strategies include the use of melanin-specific antibody responses and C-type lectins like the newly discovered melanin-specific MelLec receptor.