Aspergillus fumigatus is an opportunistic filamentous fungus that is currently the most frequent cause of invasive fungal disease in immunosuppressed individuals. Recent advances in our understanding of the pathogenesis of invasive aspergillosis have highlighted the multifactorial nature of A. fumigatus virulence and the complex interplay between host and microbial factors. In this review, we outline current concepts of immune recognition and evasion, angioinvasion and angiogenesis, secondary metabolism and the fungal stress response, and their respective roles in this often lethal infection.