Drugs are non-peptide antigens that can be recognized by specific T cells. It has been thought for many years that small molecular compounds can only be stimulating for T cells after covalent binding to MHC-embedded peptides. As most drug-specific T cell clones can react to glutaraldehyde fixed antigen presenting cells (APC), recognition of drugs by specific T cells does not require prior uptake and processing of haptenated proteins by APC. In fact, activated T cell clones can recognize drugs associated with the MHC-peptide complex in a non-covalent way. Such a binding is reminiscent of superantigen stimulations of T cells.