Lyssa was born from Night itself, or so the tragedians told it. In Euripides' Heracles, she introduces herself as the daughter of Nyx, the primordial goddess of darkness, and the blood of Ouranos, the Sky, whose castration by his son Kronos had stained the cosmos with a violence that would never fully wash away. In another tradition, recorded by the Roman mythographer Hyginus, she was the child of Aether, the upper air, and Gaia, the Earth, a union of the highest and lowest elements that produced a spirit of pure, ungovernable force. She was not one of the great Olympian goddesses who received temples and processions; she was a daimon, a personified power, one of the many spirits who moved through the Greek world as agents of divine will rather than objects of worship. Her sisters were the Maniai, the goddesses of mania and obsessive madness, and her Roman equivalents were Ira, Furor, and Rabies, names that made her nature unmistakable in any tongue.

Her most famous appearance came in the tragedy of Heracles, the hero who had completed his twelve impossible labours and returned to Thebes to find his family threatened by the tyrant Lycus. Heracles killed Lycus and was preparing to purify himself of the blood-guilt when Hera, who had hated him since before his birth because he was the son of her husband Zeus and the mortal woman Alcmene, decided that his triumph would not stand. She sent Iris, the rainbow messenger of the gods, to summon Lyssa from the underworld, and the two of them descended upon Heracles' house like a storm. Iris gave the order, and Lyssa, though she hesitated at first, arguing that Heracles was a pious man who had restored the worship of the gods when impiety had caused it to decline, accepted the command. She was a servant of the gods, not a rebel, and when Hera commanded, she obeyed.

What followed was one of the most horrifying scenes in all Greek tragedy. Lyssa entered Heracles' mind like a disease entering a wound. She did not possess him from without; she unravelled him from within, turning his strength against those he loved most. Heracles saw his children as enemies, his wife Megara as a monster, and his own home as a fortress to be stormed. He seized his bow and his club, the weapons he had used against the Nemean Lion and the Hydra, and turned them upon his family. The chorus heard the sounds from outside: the crash of the roof, the bellowing of a man turned beast, the screams of the dying. When the madness passed and Heracles woke to find the bodies of his wife and sons around him, Lyssa was already gone, her work complete, leaving only the ruin she had made. The poet described her as a virgin without hymeneals, a creature who had never known love or mercy and who brought only destruction to those she touched.

Lyssa appeared again in the story of Actaeon, the young hunter who stumbled upon the goddess Artemis bathing in a forest pool on Mount Cithaeron. Artemis, the virgin goddess of the hunt, was so outraged by the intrusion that she transformed Actaeon into a stag, stripping him of his human form in an instant. But the transformation alone was not enough for the goddess's vengeance. She called upon Lyssa, or in some versions Lyssa came unbidden, and the spirit of frenzy descended upon Actaeon's own hunting hounds. The dogs, who had been raised by their master from puppies, who had slept at his feet and eaten from his hand, were driven into a rabid fury by Lyssa's sting. They caught the scent of the stag and gave chase, and when they brought him down they tore him apart with their teeth, not recognising the human mind that screamed behind the deer's eyes. In Greek vase painting, Lyssa is shown standing beside the dying Actaeon, a small figure wearing a short skirt and a cap made from the head of a dog, the animal whose madness she most perfectly embodied. The image is one of the most chilling in ancient art: the spirit of rabies made visible, watching her handiwork with the calm indifference of a force of nature.

In other myths, Lyssa served different masters with the same ruthless efficiency. In Aeschylus' lost play the Xantriai, she was sent by Dionysus, the god of wine and ecstatic frenzy, to drive the Minyades mad, three sisters who had refused to join his rites and who were punished by being turned into bats or driven to tear their own children apart. In the Dionysiaca of Nonnus, the 5th-century CE poet, she appears as a companion to Ares, the god of war, riding beside him on the battlefield and infecting warriors with a battle-fury so intense that they lost all distinction between friend and foe. Wherever there was violence that exceeded the normal bounds of human anger, wherever a man killed what he loved or a dog turned upon its master, the Greeks saw the hand of Lyssa, the daughter of Night, the sting of madness, the spirit who made monsters of men.