Aspergillus fumigatus is a saprophytic fungus commonly found in soil and compost piles. In immunocompromised patients it takes on a sinister form as a potentially lethal opportunistic human pathogen. We currently have a limited understanding of the in vivo growth mechanisms used by A. fumigatus during invasive pulmonary aspergillosis (IPA). The ability of A. fumigatus to adapt to various microenvironments encountered during growth in the human host may explain why A. fumigatus is the most frequently occurring opportunistic pathogenic mold. The transcriptional and metabolic responses to changing microenvironments found in the mammalian lung require the activation of pathways implicated in resistance to unique stresses. Thus, the production of primary metabolites in vivo may give clues to the critical pathways used by A. fumigatus to cause disease in human hosts. We recently have identified primary metabolites in the mammalian lung typically associated with fungal growth under hypoxic environments suggesting that A. fumigatus may encounter low oxygen tensions during IPA. These and other studies on A. fumigatus metabolism are the focus of this review.