The menstrual cycle is a complex and tightly coordinated cycle involving hormones, paracrine, and autocrine factors that all work in harmony towards a goal of releasing a single mature oocyte into a uterus primed for implantation. It is crucial for learners to obtain a solid understanding of this complex cycle and identify how its dysfunction contributes to many clinically relevant pathologies. This chapter follows the case of a reproductive-aged female who has experienced a dysfunction in her menstrual cycle. By the end of the chapter, one should have a solid understanding of the causes behind primary and secondary amenorrhea, be able to identify how disruptions in the hypothalamic-pituitary-ovarian (HPO) axis contribute to disease processes, and obtain a working knowledge of how one starts to evaluate gynecologic disorders.