Shadowhunters, are also known as Nephilim. They are a secretive race of beings who are humans born with angelic blood. They are warriors, appointed long ago on Earth by Angel Raziel. Shadowhunters often die young as their fight against demons kill off many of them in battle. The traditional color of mourning among the Nephilim is white, contrary to the mundanes' typical black, which is their color of fighting, for their clothes, and red for runes.

They were appointed specifically to control over the Shadow World, as well as preside over the demons and Downworlders who inhabit it. They have fought the demonic forces valiantly for well over the span of a thousand years, creating their own culture and civilization within human society. Their mandate is to keep the peace in the Shadow World and keep it hidden from the mundane world while protecting the inhabitants of both worlds.

Despite their ancestry, Shadowhunters are mortal and therefore vulnerable to old age and death; however, their angelic blood endows them with special abilities that allow them to achieve feats beyond humanly possible through the application of angelic runes, and other skills attributed by the angel blood.

In the Bible, the Nephilim were the offspring of humans and angels, although it is unknown if they really existed or not. According to the Nephilim, the Angel Raziel was called by a crusader named Jonathan, he begged Raziel to help save humanity. Seeing that his wish was true and pure, the angel obliged and mixed his blood Jonathan’s in the Mortal Cup, a mixture he let Jonathan drink. Raziel then gave Jonathan the other two Mortal Instruments, the Gray Book, and the fitting name of Shadowhunter as a symbol of his transformation. More men and women drank from the cup and became Nephilim warriors themselves. They soon became known as Shadowhunters, after Jonathan, the first of their kind. Their children, and their children's children, inherited their parents' angelic blood and became Nephilim themselves. Throughout time, they came to the first step of peace negotiations with the Downworld populace.