Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) - stimulator of interferon genes (STING) signaling pathway plays the critical role in the immune response to DNA. Pharmacological modulation of the STING pathway has been well characterized both from structural and functional perspectives, which paves the way for the drug design of small modulators by medicinal chemists. Here, we outline recent progress in studies on the STING pathway, the structure and biological function of STING, the STING related disease, as well as the rationale and progress in the development of STING modulators. Our review demonstrates that STING is a promising drug target, and providing clues for the discovery of novel STING agonists and antagonists for the potential treatment of various disease including microbial infectious diseases, cancer, and autoimmune disease.