Members of the tumour necrosis factor (TNF) superfamily have been implicated in a wide range of biological functions, and their expression by cells of the immune system makes them appealing targets for immunomodulation. One common theme for TNF superfamily members is their coordinated expression at the interface between antigen-specific T cells and antigen-presenting dendritic cells and, by virtue of this expression pattern, TNF superfamily members can shape T cell immune responses. Understanding how to manipulate such functions of the TNF superfamily may allow us to tip the balance between immunity and tolerance in the context of human disease.