Host immunity is essential in facilitating the eradication of infection. However, immunological recovery and an imbalance characterised by either suboptimum or excessive expression of immune responses can also be harmful to the host. Inflammatory responses triggered by rapid resolution of immunosuppression can lead to a series of localised and systemic reactions, termed immune reconstitution syndrome (IRS), that are often misconstrued as failure of specific antifungal therapy to eliminate the offending fungal pathogen. Recognition of IRS has become increasingly relevant in the context of our current use of potent immunosuppressive agents and immunostimulators that allow rapid manipulation of the immune system. Whereas the conceptual principles of IRS underscore the adverse effects of an overzealous and dysregulated immune response, they also support a role of immunotherapies to augment immunity if induction of endogenous responses is inadequate for the control of infection.