The group was founded by Osiris, the "Resurrected King". Though many Kindred do not believe they exist today during the Final Nights, those who are an authority on the Children of Osiris do believe they exist in secret, under the direction of Khetamon, the "Grand Undying King". They are known to practice a Discipline unlike any other, called the Bardo, which allows a vampire to have control over the Beast within. All their members come from other clans, or are Caitiffs. Thus, there are hardly any neonates in their ranks. Few elders join, as the Children require a high level of Humanity. Their arch-nemeses are the Followers of Set.
Sometime around 4000 BCE, the Founder of the Children, Osiris, went on a spiritual journey, likely to India, to investigate deep mystical enlightenment and practice ancient methods of meditation. He was compelled to take control over the "Beast" within, as he did not accept his Embrace well. It probably took a millennium to develop and master this control, which became a new Discipline, known as Bardo. Bardo allows its practitioners to retain some degree of humanity, redeem other vampires and ward off evil; it even has the power to resurrect a vampire from Final Death. After gaining mastery of it, Osiris preached this newfound way to other Kindred, thus forming the Children of Osiris bloodline. Osiris granted his Children knowledge of Bardo, a discipline very difficult to master, whose secrets are never shared with outsiders.
Because Bardo gives a vampire a sense of humanity, it is greatly looked down upon by most vampire clans, especially the Followers of Set, who despise the thought of "preserving humanity"; the Children view the Followers as utter evil that needs to be destroyed. Thus, both groups have waged private wars for millennia as their Founders slumber. In one such battle between Set and Osiris, when the Pharaohs ruled, Set forced his brother and childe into torpor through magic, then rent the body into pieces and scattered the mystically-preserved limbs across the kingdom of Egypt to prevent Osiris waking again. Osiris' wife and first childe, Isis, found the parts and re-assembled them, then together with the other Children used Bardo to restore Osiris to unlife. However, Osiris' "rebirth" came at the cost of sterility - Osiris returned unable to sire childer or create ghouls. His Children pay homage to their Founder's change by refraining from the Embrace, instead taking in Caitiff and other castaways to expand their numbers.
After the invasion of the Sixth Great Maelstrom in the Underworld, Osiris returned to Earth to transform all of his faithful Children into humans while granting them knowledge of a new Spell of Life. This allowed them to join the ranks of the Undying. The few unfaithful, among the Children, were destroyed. To many Kindred, the Children are thought to be extinct. However, other sources indicate that they do exist as a secret organization, still making use of the power of Bardo.
The Children of Osiris believe in Egyptian folklore, and see their role as being a holy one, combating the "darkness" of the Setites by the "light" of Osiris. Since their Founder had lost his ability to sire, after being dismembered by Set, the Children are generally forbidden from granting the Embrace. Osiris' "embracing impotence", is a parallel to an Egyptian myth, where Isis was unable to locate his member when she reassembled his body. Only through the use of Bardo, can the vampire discipline oneself from any temptation to Embrace. Therefore, their ranks are comprised of vampires recruited from other clans, bloodlines, and caitiffs. Those who join are expected to have a high level of Humanity.
The Children prefer secluded, mystical locations. They live communally in havens called Temples, the primary location for learning their trademark Discipline. Currently, their Grand Temple is located in a secluded mountainous region in Nepal. Their Grand Master is called the "Undying King", and his consort, sometimes called the "Daughter of Isis". He leads the others in his example of asceticism. Hierarchy usually comes in levels of respect, gained through degree of adherence to the discipline of Bardo. However, their attainment of the discipline is never forced. It must be balanced and learned by example in an effort to have a pure existence in their most impure form. The Children put forth no illusions about themselves. As a child develops in their commune, they gain a sense of vision and penitence, often become perfectionists.
The Children of Osiris are one of the clearest examples of the First Edition having a rather forgiving attitude toward vampires, seen more like a sect of "good guy" vampires than the early Camarilla or Inconnu. They were rarely mentioned in Second Edition material, though Mummy mentions Khetamon and the alliance between the Undying and the Children. With the Revised Edition, the Children clearly no longer fit in with the themes and mood of Vampire: The Masquerade. They were officially removed from the metaplot of Mummy: The Resurrection, at least as being vampires. According to Mummy: The Resurrection, Osiris judged the Children of Osiris and made them human again, save for those that were not true to Ma'at. Those that fell short were instead consumed in solar fire. The "vampire priests of Children of Osiris" are mentioned in Sorcerer Revised Edition in the description of the Children of Osiris sorcerers' organization. They are believed to be recently eliminated by the Followers of Set and also have a limited presence in Cairo by Night, in the form of just one mortal character.