Methotrexate for treatment of ectopic tubal pregnancy has become an accepted alternative to surgical options. Methotrexate is a folic acid analog that interferes with DNA synthesis. Protocols using planned multiple doses of methotrexate alternating with citrovorum rescue factor and one protocol using only a single planned dose are both currently used in the treatment of ectopic pregnancy. In remains unclear which protocol is superior. This article reviews the indications, contraindications, and specifics of using methotrexate for this purpose. Also reviewed are predictors of success and management of usual complications associated with methotrexate therapy.