Helminths are extraordinarily successful parasites due to their ability to modulate the host immune response. They have evolved a spectrum of immunomodulatory molecules that are now beginning to be defined, heralding a molecular revolution in parasite immunology. These discoveries have the potential both to transform our understanding of parasite adaptation to the host and to develop possible therapies for immune-mediated disease. In this review we will summarize the current state of the art in parasite immunomodulation and discuss perspectives on future areas for research and discovery. Parasitic helminths modulate the immune system, preventing immune-mediated ejection and suppressing immune-mediated diseases. In this review, Maizels and colleagues describe the secreted molecules by which parasites achieve this and the methods by which these molecules have evolved.