The four Sons of Horus, generally considered semi-divine genii, were given the duty of looking after the organs of Osiris, so that he would be whole in the afterlife. Their popularity extended from the Old Kingdom to the Greco-Roman Period. Along with looking after the organs of the dead, they were assigned the four cardinal directions. Imseti governed the South, Hapi the North, Duamutef the East, and Qebehsenuef the West. Also, Hapi and Duamutef were paired and associated with Lower Egypt, especially the city Buto. Imseti and Qebehsenuef were guardians of Upper Egypt, in particular, the city of Hierokonpolis. Because of their duty to Osiris, they became the guardians of the organs of all who have died. Imseti guarded the liver, Duamutef the stomach, Hapi the lungs, and Qebehsenuef the intestines. These were not the only body parts the Sons of Horus were responsible for. Hapi and Duamutef looked after the hands, while Imseti and Qebehsenuef looked after the feet. Of course, the Sons of Horus were not without their own guardians. Neith looked after Duamutef, Isis (Aset) guarded Imseti, Nephthys (Nebt-Het) was responsible for Hapi, and Selket watched over Qebehsenuef. The genii were mentioned many times in The Book of Going Forth By Day/The Book of the Dead, and The Book of Gates, in which they fight the evil serpent, Apep/Apophis.

Their depictions vary over time. The most common representation comes from canopic jars. These jars, which held the organs of the deceased, were capped with the heads of the Sons of Horus to ensure their guardianship. However, it was only until around the 18th Dynasty that the semi-divine figures were no longer represented with human heads. From this time on, Imseti alone remained human-headed, while Hapi assumed the baboon-headed form, Duamutef the jackal, and Qebehsenuef a hawk.