Prostaglandin antagonists, with their pharmacological effects, are well-known drugs capable of treating widely diffused illnesses, including pain and inflammation disorders. In recent years, a major research focus has been devoted to the identification of agents able to selectively antagonize each receptor with which prostaglandins interact. This review attempts to give a broad overview of molecules capable of selectively blocking the prostaglandin PGE2 EP4 receptor. Further therapeutic applications and uses have also been disccussed, including the first drug candidate to have reached clinical trials within the last few years.