Endometriosis is a chronic condition affecting millions of women worldwide, characterized by the growth of uterine-like tissue outside the uterus. One of its key underlying issues is progesterone resistance, a state where the body’s tissues fail to respond adequately to progesterone—a hormone essential for regulating the uterine lining’s growth. This article explores the mechanisms behind progesterone resistance, its interplay with estrogen receptors, environmental factors, and emerging treatment strategies.