For thousands of years, mycobacteria have evolved with vertebrates by parasitizing their immune system. Their intraphagocytic lifestyle enables an escape from humoral immunity, while providing an extraordinarily rich and durable source of T-cell stimuli. Macrophages can chew out mycobacterial cell wall antigens which, once associated with polymorphic MHC molecules, are presented on their cell surface, Upon recognition of these antigens, the reactive T lymphocytes trigger effector responses such as immune help or bacterial killing that may ultimately protect against infection. So far, the antigens specifically recognized by the T-cell receptor for antigen (TCR) were thought to correspond exclusively to small peptidic fragments processed from microbial proteins. However, recent studies have revealed other types of antigenic molecules from mycobacteria, but also from other sources, which stimulate strong T-cell responses in humans and in mouse models. These non-peptide antigens can be recovered in different structural classes: aliphatic lipid or glycolipids and phosphoantigens. Beside mycobacterial nonpeptidic T-lymphocyte reactivity, another immunological context (allergy) involving T lymphocytes stimulated by an aromatic glycolipid was recently demonstrated (figure I). This article will briefly review these three distinct categories of non-peptide ligands recognized by T cells, which involve atypical pathways of antigen recognition.