Where we are losing, and where cryptococcal disease burden is centred, is in individuals with compromised immune systems. Evidence from all areas, clinical, animal models and in vitro experiments, points to the central importance of the macrophage/T cell axis. Immune defects in T cell development (blood proliferative disorders), numbers and functionality (HIV infection, immunosuppressant treatment) and signalling (antibodies to TNFα) all lead to increased risk of disseminated cryptococcal infection.