Lomentospora prolificans is an emerging opportunistic pathogen that primarily affects immunocompromised individuals leading to disseminated disease with high mortality rates while also causing infections in healthy populations. Successful recovery from infection is difficult due to high rates of intrinsic resistance to antifungals. Rapid and readily available diagnostic methods, aggressive surgical debridement wherever appropriate, and effective and timely antifungal treatment are the pillars for successful management. Future research will need to clarify the environmental niche of the fungus, further investigate the pathophysiology of infection and define species-specific therapeutic targets.