This chapter discusses the physiology of the luteal phase both in natural and stimulated cycles, with emphasis on the current evidence-based approaches for luteal phase support in assisted reproduction. Progesterone (P) and estrogen (E) are required to prepare the uterus for embryo implantation and to modulate the endometrium during the early stages of pregnancy. A meta-analysis of all available quasi randomized trials showed that the use of gonadotropin-releasing hormone (GnRH) agonists increased in vitro fertilization (IVF) pregnancy rates by 80-127 percent in women who responded normally to exogenous gonadotrophins. It was shown that the addition of a high dose of E2 to daily P supplementation significantly improved the probability of pregnancy in women treated with a long GnRH agonist protocol for controlled ovarian stimulation. Vaginal P supplementation before embryo transfer may be useful in quieting uterine contractions and thereby reducing embryo displacement.