Aspergillus fumigatus is a medically important human pathogenic fungus. It can cause various diseases such as serious allergic reactions and life-threatening, invasive infections. Proteome analyses massively contribute to elucidating host-pathogen interactions. Here, we describe challenges to analyze host-pathogen interactions using mass spectrometry-based proetomics; we provide insights into our research findings and current understanding about the role of proteins from both the fungus and human immune cells during infections.