Dihydroxynaphthalene melanin (DHN-melanin) is an integral component of the conidial cell wall surface, which has a central role in the pathogenicity of the major human airborne fungal pathogen Aspergillus fumigatus. Although the biosynthetic pathway for A. fumigatus DHN-melanin production has been well characterized, the molecular interactions of DHN-melanin with the immune system have been incompletely understood. Recent studies demonstrated that apart from concealing immunostimulatory cell wall polysaccharides, calcium sequestration by DHN-melanin inhibits essential host effector pathways regulating phagosome biogenesis and prevents A. fumigatus conidia killing by phagocytes. From the host perspective, DHN-melanin is specifically recognized by a C-type lectin receptor (MelLeC) present in murine endothelia and in human myeloid cells. Furthermore, DHN-melanin activates platelets and facilitates opsonophagocytosis by macrophages via binding to soluble pattern recognition receptors. Dissecting the dynamics of DHN-melanin organization on the fungal cell wall and the molecular interplay with the immune system will lead to a better understanding of A. fumigatus pathophysiology.