Prostaglandin preparations have been the traditional approach to second trimester abortions for at least 40 years, and misoprostol recently has gained an almost “standard of practice role in obstetrics. Although many applications of misoprostol are still off-label, after more than 1,000,000 women have been treated with misoprostol all over the world, a broad base of knowledge has accumulated on the efficacy and safety of this medication. The purpose of this paper was to review the evidence supporting the different applications of misoprostol in obstetrics. The update includes a short incursion in the pharmacokinetics of misoprostol, connecting the biological plausibility with the evidence generated by clinical trials. The experience with misoprostol indicates that efficacy and side-effects are dosedependent, the practitioner having to navigate the tightrope between ineffective action and hyperstimulation. Variables relative to the technique of administration of misoprostol are also discussed. The reader will derive the benefit of an organized overview on the subject, and more importantly, of practical recommendations for a safe and efficacious use of misoprostol for at least 8 indications: labor induction, cervical ripening, 1st and 2nd trimester induced abortion, missed abortion, incomplete abortion, and control of postpartum and postabortum bleeding.