Although the exact etiology of endometriosis is unknown, several hypotheses about its origin exist. Of these, Sampson's theory of retrograde menstruation is the most widely accepted. Multiple in-vitro and in vivo models have been developed to study endometriosis. Several key steps are required to establish an endometriotic implant: presence of ectopic endometrial glands and stroma, attachment of endometrial cells to the peritoneum, invasion into the mesothelium, and survival and growth of the ectopic tissue. Many of these steps are similar to those associated with neoplasia, and numerous biologic pathways are involved. It is likely that both intrinsic factors within the ectopic endometrium and permissive alterations within the host are important to the development of endometriosis.