Endometriosis is a chronic inflammatory condition characterized by the appearance of endometrial-like tissue outside the uterus, which often causes chronic pelvic pain. Recently, endometriosis was described as a systemic disease affecting both physical and mental health. It is estimated that about 190 million or 10% of reproductive-age women could be affected worldwide. Despite being underdiagnosed and understudied, it is one of the most frequent diseases in women. Symptoms of endometriosis significantly reduce the quality of life in affected individuals and include different levels of pelvic pain, dysmenorrhea, dysuria, dyspareunia, and infertility. Individuals with endometriosis often have comorbidities, including psychiatric disorders, such as anxiety disorder, major depressive disorder, and eating disorders. Research is in the early phase of discovering the molecular mechanisms linking endometriosis to mental health. Early-stage research has also proposed a hypothesis about an “endometriosis brain,” demonstrating brain activity in pain-processing regions. This chapter explains the link between endometriosis and mental health based on epidemiological, genetic, and neurobiological evidence. In addition, endometriosis research is illustrated with a case-study example of a recent endometriosis study investigating the molecular link to selected mental health illnesses.