Mast cells have been suggested to be major effector cells in the immune response to infection with helminths. It is now clear, however, that mast cells are heterogeneous and have a diversity of important functions. In this review, Timothy Lee, Mark Swieter and Dean Befus point out that much of the confusion about the role of mast cells in immunity stems from methods and interpretations which are inadequate for the diversity of roles played by these cells in host responses to parasites. Classical histochemistry may fail to reveal active mast cells, and studies using chemical antagonists are difficult to interpret until we know more about the action of the drugs. The authors show that current research is extending our knowledge of mast cell heterogeneity, and helping to define the powerful array of mediators that they can use to orchestrate the immune response to helminth infections.