Second-trimester abortions are most commonly performed in the United States via dilation and evacuation; however, there are instances in which the use of systemic abortifacients is necessary. Lack of trained staff to perform late abortion procedures, fetal anomalies, and patient preference are important considerations when selecting the method of termination. Second-trimester abortions with misoprostol-only protocols require higher doses, side effects are more common, and the time to complete the abortion is longer in comparison to mifepristone-misoprostol combinations. Feticidal agents are recommended to avoid transient fetal survival. This chapter will review medical induction methods between gestational ages of 14 and 24 weeks that are commonly used in the United States.