Endometriosis is a chronic, estrogen-dependent, inflammatory disorder that affects ~10% of reproductive-aged women. The condition, characterized by the presence of endometrial glands and stroma outside of the uterine cavity, is multifactorial and highly recurrent, and causes chronic pelvic pain and other morbidities (e.g., depression, asthma, and migraines) that significantly diminish quality of life. The disease is linked to immune dysfunctions, infertility, and increased risk for ovarian and other (e.g., breast and endometrial) cancers. Its pathophysiology is poorly understood but is considered to have a significant genetic component and may involve abnormal endometrial epithelial progenitors. The histological diagnosis of endometriosis may be compromised by the cellular complexity and heterogeneity of the endometriotic foci which can manifest a spectrum of lesions with distinct and atypical features of stromal and glandular components. Moreover, signs and symptoms of endometriosis remain nonspecific, and a current lack of predictive noninvasive biomarkers precludes early diagnosis. This chapter aims to provide current understanding of the etiology, pathogenesis, and clinicopathologic features of endometriosis, and how emerging information from state-of-the-art technologies may be exploited for the diagnosis, management of symptoms, and therapy in women with this condition.