CD1 proteins constitute a third class of antigen-presenting molecules. They bind lipids rather than peptides, and the T cells reactive to lipids presented by CD1 have been implicated in the protection against autoimmune diseases and infectious microorganisms and in the immune surveillance for tumors. Thus, the ability to identify, purify, and track the response of CD1-reactive cells is of paramount importance. Previously existing methods for identifying these T cells were not based on TCR specificity, and therefore the data obtained by these methods were in some cases difficult to interpret. The recent generation of tetramers of alpha-galactosyl ceramide (alpha-GalCer) with CD1d has already permitted significant insight into the biology of NKT cells. Tetramers constructed from other CD1 molecules also have been obtained during the previous year. Collectively, these new reagents promise to greatly expand knowledge of the functions of lipid-reactive T cells, with potential use in monitoring the response to lipid-based vaccines and other treatments and in the diagnosis of autoimmune diseases.