Clomiphene revolutionized the management of infertility in 1967 when it was approved for treatment of anovulation due to polycystic ovaries (PCO). The pharmacokinetics and pharmacodynamics of clomiphene explain its characteristic actions. After ovulation induction with clomiphene, serum progesterone and estradiol serum levels are increased during the luteal phase of the cycle in a direct dose-response relationship. Ultrasound of the ovaries should always be performed before initiating clomiphene treatment for the first time to rule out preexisting ovarian neoplasm, endometriomas, and persistent corpus luteum cysts to evaluate the number and size of antral follicles. Progesterone is used to confirm ovulation to determine if the dose of clomiphene is sufficient. Pregnancy rates may be increased in clomiphene cycles by increasing the number of follicles that develop, by improving endometrial conditions and cervical mucus, and by intrauterine insemination (IUI) when numbers of sperm on a postcoital test are low or absent.