Reports of Aspergillus' azole resistance are emerging, and resistance is now recognised as a cause of treatment failure. The scope of this article is to describe the problem of resistance in Aspergillus: the epidemiology, clinical impact and the underlying molecular mechanisms. In patients with acute invasive aspergillosis, the probability that the patient harbours a resistant strain depends on the emergence of resistant strains in the environment (acquired resistance due to CYP51A mutations and/or natural resistant Aspergillus species). As environmental pan-azole resistance of Aspergillus fumigatus is reported in increasing numbers in the Netherlands, surveillance is warranted. Voriconazole currently remains the first line therapeutic agent for invasive aspergillosis in Belgium. In chronic (and chronically treated) Aspergillus infections,"in-patient" resistance development is possible, especially in the setting of aspergilloma. Culturing an isolate during therapy should therefore be a trigger to test susceptibility.