Rectally administered medications are essential in palliative medicine, particularly in the last days of life. They are underutilized. The pharmacology of rectally administered medications relates not only to the medication but also to the suppository base, additives, drug ionization, pKa, absorptive surface of the rectum, and rectal health. The pharmacokinetics may differ from those of orally administered medications owing to reduced hepatic first-pass clearance. In this review the pharmacology of rectally administered palliative medications is reviewed and the use of individual drugs is outlined.