Invasive aspergillosis (IA) is a increasing cause of morbidity and mortality among immunocompromised patients. Lately aspergillus infections are reported to occur also in patients without typical predisposing factors. This includes among others, patients with COPD, livercirrhosis, diabetes and those treated in Intensive Care Units. The impact of IA in these, apparently less immunocompromised patients is, however not well known. There has been a development towards better diagnostic tools, and new antifungals such as voriconazole and echinocandins for the treatment of IA. Despite these advances, invasive aspergillosis remains an underdiagnosed disease that often has an insidious onset but a fatal outcome. Mortality due to invasive aspergillosis though treated, still ranges from 30-80%, depending on the stage of the infection and the underlying disease of the patients. There is a lack of data on the applicability of these new diagnostic tools to the population of less immunocompromised patients and the optimal treatment for this group.Because of the high mortality there is a growing interest for the use of antifungal combination therapy, salvage therapy, prophylaxis and agents affecting new targets. In this paper we present a fatal case with IA and discuss challenges related to early diagnosis and treatment.