Besides classic T cell-derived T-helper type 2 (Th2) cytokines such as IL-4, IL-5 and IL-13, tissue-produced cytokines such as thymic stromal lymphopoietin, IL-25 and IL-33 are now recognized as important contributors to allergic inflammation. IL-33 is produced by various tissue dwelling cells and broadly enhances allergic inflammation through its effects on hematopoietic cell types. The environmental or endogenous triggers that provoke IL-33 cellular release may be associated with infection, inflammation or tissue damage. This review summarizes the wide range of documented IL-33 activities on human cellular mediators of inflammation as well as genetic evidence that IL-33 contributes to disease. Finally, there will be a discussion of still unanswered questions regarding the mechanisms by which cytokine activity is generated and IL-33's relationship with other Th2-associated cytokines.