Accelerator is the most powerful Psychic in Academy City. A sadistic boy about the same age as Tōma, he has an ability called "Vector Change", a form of telekinesis allowing him to change the vector values of anything he touches due in part of having a thin coat of AIM fields surrounding his body. This ability allows Accelerator perform feats such as reversing the blood flow inside a person's body, increasing the wind velocity around him to create a massive plasma storm, and blocking sound. His ability is automatic, which means that he must consciously allow gravity to affect him and that his body blocks all ultraviolet radiation, resulting his albino appearance (white hair and pale skin) because his body is unable to make melanin. The automatic nature of Redirection also prevents the use of projectiles (like bullets) and explosives (like bombs) against him.

Johan Liebert is the titular "monster" of the story who serves as the principal antagonist; the mystery of his past is the main focus of the plot. He has been called a monster, the next Hitler and even the Devil himself. Johan Liebert was shot in the head at a young age but saved from death by Dr. Tenma. Because of this, he regards Dr. Tenma almost as though he was his father. He claims to have a deep love for his twin sister and is shown to have some loyalty to her. He has spent portions of his life in different places under different aliases. He possesses an extraordinary level of charisma and intelligence, as well as being cunning, manipulative and deceitful. While he is shown to be kind, compassionate, and loving to children, he can be cold and very cruel. He uses his gifts to cruelly manipulate and corrupt others, often with no apparent end than to cause suffering and destruction. His goal, as he stated when he was young, is to be the last one standing at the end of the world.

Guts is the protagonist of the story. A tall, muscular male with a huge sword called the Dragon Slayer, a prosthetic left forearm that has a magnetic grip, and also conceals a cannon. Guts is a tragic hero; he is born as one who may be able to struggle against Causality, but seemingly unable to affect it on a large scale.

Oga is easily agitated and is always willing to fight, unless it will bring out the Zebub spell. He appears to have his own skewed idea of what a 'man' should be like, and attempts to pass on these ideals to Be'el. Despite being called evil by almost every character of the series, he has shown to have a calmer and, if only slighlty, warmer side to him, shown when he speaks with Hilda about his position as Be'el parent and assuring Lamia that if Be'el ever got sick again he would call her immediately.

A small-time criminal who was in a gang with his best friend, Harry McDowell, along with three other close friends. After these three were killed, Brandon and Harry joined Millennion, a powerful mafia-type organization formed by Big Daddy. Brandon was trained by the Millennion's Bear Walken to be a sweeper (hitman), eventually forming his own elite sweeper unit within Millennion called True Grave. Even as Harry rose to power, Brandon remained loyal to Big Daddy for Maria's sake.

Xanxus is the current Leader of the Varia, Vongola IX's adopted son, and the main antagonist of the Varia Arc. He was born into poverty with just his mentally ill mother. His mother discovered his Dying Will Flame when he was very young and brought him to Vongola IX. When she and Xanxus confronted the 9th, he took Xanxus and placed his scarf around him, agreeing that he was indeed his son even though he had never seen this woman nor her son before. During the Varia Arc, he and Tsuna battle for the Sky Vongola Ring and the position of the 10th Vongola Boss. Later, in the Future Arc, he remains the leader of the Varia and leads a raid against the Millefiore, taking their Headquarters. He battles against one of the Fake Funeral Wreaths as well and wins, showing that he has grown much stronger in the Future.