Abnormal uterine bleeding (AUB) is one of the most common reasons patients present to the gynecologist [1]. Fibroids are a major cause of abnormal uterine bleeding within the PALM-COEIN classification system, with “L” standing for leiomyoma [2]. Fibroids occur in multiple locations throughout the uterus (Figure 7.1), and heavy menstrual bleeding due to fibroids can result in severe anemia and decreased quality of life [3]. Despite a century of research on fibroids, there is no clear consensus on the mechanisms underlying uterine bleeding secondary to fibroids. This chapter will summarize the evolving hypotheses regarding the pathophysiology of fibroid-related bleeding.