Despite the availability of new antifungal compounds, morbidity and mortality of invasive aspergillosis are still unacceptably high, in particular in immunocompromised patients such as patients with hematological malignancies or allogeneic hematopoietic stem cell or solid organ transplant recipients. Over the last decades, our knowledge of the immunopathogenesis of invasive aspergillosis has greatly advanced. This, in turn, provided critical information to augment host immunity against fungal pathogens. Potential approaches for enhancing the host immune system in the combat against Aspergillus include the administration of effector and regulatory cells (e.g., granulocytes, antigen-specific T cells, natural killer cells, dendritic cells) as well as the administration of recombinant cytokines, interferons and growth factors (e.g., interferon-γ,granulocyte- and granulocyte-macrophage colony stimulating factor) and various vaccination strategies. Although promising results are reported on in vitro data and animal studies, current data are too limited to allow solid conclusions on the risk and the benefit of these strategies in the clinical setting. Therefore, the real challenge in the future is to perform appropriately designed and powered clinical trials. These require international, multi-center collaboration, but may ultimately improve the outcome in immunocompromised patients suffering from invasive aspergillosis.