Humans are mortal beings that populate the planet Earth and are the children of Adam and Eve and later become the descendants of Cain and Abel. They are considered by God to be His last and greatest among all His creations. Each human has a soul, and, upon their death, will face judgment to determine where their soul will go in the afterlife. Those who have broken God's laws and/or lived a life of evil are to be sent to Hell for punishment, while most others will find eternal solace in Heaven. While punishment in Hell is stated on several occasions to be eternal, humans can be redeemed from Hell by angels.

Humans who die will find a Reapers waiting to escort them away, presumably to face their judgment. Some humans with unfinished business, uncertainty about their own death, intense emotional ties to the physical world or who have evaded the Reaper sent to collect them, may return to Earth as ghosts or vengeful spirits.

Humans and their souls are vulnerable to certain supernatural forces that could weaken, strengthen or modify them in many conceivable ways. For example, human souls sent to Hell can be corrupted into demons through years of torture and degradation and there are many different types of monsters that can transform a human into the said monster.

Humans are also capable of being hosts or vessels for various supernatural creatures. Some types of being which seek to possess a human may require the human's consent. More often than not, however, humans are incapable of preventing forced possession without mystical protection, although particularly strong-willed humans are able to partially resist the demons possessing them.

Humans can also become abnormally strong and gifted beings known as Deviants, beings whom are born with extraordinary powers that range from telekinesis, telepathy, geokinesis, thermokinesis, umbrakinesis, and many more. These types of species of humans are born with these abilities through a gene known as the muta-gene, which can alter the DNA of human to the point where they attain abilities not naturally found in an ordinary human.

Many supernatural beings, regardless of their origin and alignment, look down upon humans because of their mortality, fallibility and physical frailty. Especially beings like Lucifer who views them as savage and murderous creatures while others like deities simply view them as expendable resources or play things. Even other angels at times frown upon humans for their actions on Earth.