Interleukin-13 (IL-13) as a pleiotropic cytokine acts through the IL-13Ra1/IL-4Ra complex to induce activation responses which contribute to the inflammatory diseases. Genetic polymorphisms in IL-13 and its receptor components have been proved to be associated with higher disease prevalence rates. Animal models such as in IL-13 deficient mice and transgenic animals also have been confirmed the critical role of this cytokine in the immune responses, mostly by IL-13 neutralization and IL-13/IL-4 dual neutralization strategies. This review highlights IL-13 structure as well as its pivotal roles in the normal physiologic and pathologic states. It is followed by a section on the recent findings on IL-13 receptors and signalling mechanisms to briefly summarize its functions in the immune systems. IL-13 roles in the human diseases such as asthma, systematic sclerosis, and some inflammatory diseases are described concisely. Finally some of the ongoing therapeutic applications are presented to comprehensively review IL-13 mediator roles.