Toll-like receptors are key to pathogen recognition by a host and to the subsequent triggering of an innate immune response. Experimental and clinical evidence shows that defects in Toll-like receptors or in signaling pathways downstream from these receptors render hosts susceptible to various types of infection, including aspergillosis. Patients receiving an immunosuppressive regimen, including corticosteroid therapy or cytotoxic chemotherapy, are also susceptible to infections. Aspergillus fumigatus is an opportunistic pathogen that infects the lungs of immunosuppressed hosts. Here, we review the evidence that experimental inactivation of various Toll-like receptors and of their signaling pathways may worsen cases of invasive pulmonary aspergillosis. Moreover, the literature clearly indicates that the type of immunosuppression is very important, as it influences whether or not Toll-like receptors contribute to infection. The involvement of Toll-like receptors, based on the immunological status of the patient, should be considered if an immunosuppressive treatment must be administered.