Microbes produce a wide range of molecules that can modulate eukaryotic immune responses. These include factors that subvert protective mechanisms in order to facilitate pathogen colonization and persistence. Viral, bacterial and parasite-derived molecules have been identified that can inhibit inflammatory responses. However, in addition to the plethora of microbial factors that suppress immune responses, the most potent immune activators are also of microbial origin. These include the bacterial enterotoxins, parasite-derived excretory-secretory products and viral nucleic acids. In fact, there are examples of immune modulators that can exert either stimulatory or suppressive effects depending on the mode of delivery, dose and experimental model. There is presently great interest in the therapeutic exploitation of these factors, for example as a means to stimulate enhanced immune responses to a new generation of subunit vaccines or to inhibit deleterious immune mediated diseases. This short review, describes representative microbial immunomodulators, their modes of action and the potential for therapeutic application.