Invasive aspergillosis is a common and devastating complication in severely immune-suppressed individuals with hematologic malignancies and in hematopoietic stem cell transplant recipients. With the increase use of immunosuppressive therapies, better intensive care, and prolonged patient survival, we are experiencing a surge in the incidence of invasive aspergillosis in our critically ill patients without malignancy. In this article we discuss the epidemiology, risk factors, and clinical spectrum of invasive aspergillosis in critically ill patients without malignancy. Diagnostic methods and recommended treatments are also presented. The emphasis is placed on early diagnosis and use of new and sensitive diagnostic tools.