Fist

Fists were the weakest form of fighting, useful when no weapons were available, or when an Assassin did not wish to draw the attention of a guard.

Middle Ages
Altaïr Ibn-La'Ahad could use his fists to fight or stun enemies at any time, though they were quite ineffective against alerted or armed opponents.

Because of their rank, novice Assassins were not allowed to carry weapons, and thus needed to avoid fights or resort to using their fists. Higher-ranked Assassins also used unarmed fighting to interrogate a target, or after being caught by thugs while attempting to pickpocket throwing knives.

Using fists in a fight against civilians did not raise suspicion with the guards, who would only intervene if they themselves were attacked or if the Assassin drew their weapon during the fight while being watched by the guards.

Renaissance
Ezio Auditore da Firenze was more skilled in fist-fighting than Altaïr, and was likely taught by his brother, Federico. The two were once embroiled in a brawl against Vieri de' Pazzi and his men, where all present used only their fists.

When unarmed, Ezio could perform many different combination strikes, counter other fist-fighters, and throw sand in their faces. He also learned to disarm foes and use their weapons against them; eventually learning to kill them in one swift move right after doing so. However, Ezio could not chain together kills with his fists like he could with other melee weapons.

Fists also became a more viable option for combat when the Metal Cestus, a hard steel hand-guard, was purchased from blacksmiths.

Guards eventually learned to throw sand in Ezio's face, exactly as he could, though they could do so while still holding onto their weapons. Ezio could only perform the same move with his weapon equipped, as long as he had no bullets or throwing knives left.

Additionally, the Caserma di Alviano played host to a Fight Club, where mercenaries competed in unarmed fighting. Ezio was able to participate in the fights, by Bartolomeo d'Alviano's suggestion, in order to improve his skills with his fists.

American Revolution
Haytham Kenway and Ratonhnhaké:ton were skilled fighters, although their styles were different to Ezio's or Altaïr's. They would frequently use an environment to their advantage, such as glass bottles and breakable barrels against their enemies. Unlike Ezio, who had a more elegant style to his fist-fighting, Haytham and Ratonhnhaké:ton fought with a more ruthless and powerful form. They were more than capable of snapping bones, as well as knocking people to the floor.

Ratonhnhaké:ton was invited to join a fight club known as the Boston Brawlers, who were having a tournament at the time. Throughout several fights around the colonies, he ranked higher and higher until he was allowed to participate in the competition. At the end, Ratonhnhaké:ton became the new champion of the Boston Brawlers, but never participated in their fights following.

Modern times
Upon escaping Abstergo Industries with Lucy Stillman, Desmond Miles did not yet have a weapon, so he was forced to fist-fight the Abstergo security officers attempting to detain him.

Though his abilities were initially rather limited, over time, he was able to gain Ezio's fist-fighting skills through the Bleeding Effect. After this, he became able to perform counters and disarm his enemies.

Later, after reliving the memories of Ratonhnhaké:ton, Desmond's fighting style began to closely mimic his new ancestor's. He would fight with much more strength and could take down several guards quickly and fluidly.

Trivia

 * The achievement "Messer Sandman" could be earned by throwing sand at four guards at once; a skill that Ezio could learn from the instructor at Monteriggioni.
 * When Ezio successfully disarmed a guard and continued to use his weapon, the bottom-left hand of the Animus display remained as the fist icon, unless the Assassin had no weapon of his own. In this case, Ezio would confiscate the guard's weapon for himself.
 * Despite seemingly lethal actions, such as those resembling breaking the enemy's neck, targets defeated with fists would merely appear to be knocked out, and not count as dead.
 * In Assassin's Creed: Brotherhood and Assassin's Creed: Revelations, however, particularly during missions where full synchronization required Ezio to not kill anyone, knocking out a guard using fists would still count as a kill.
 * In the Assassin's Creed II memory "Last Man Standing," it was possible to disarm the attacking Brutes, but not the normal guards.
 * In Assassin's Creed III , knocking enemies out using fists would not count as a kill, however corner-assassinating with fists would. When Haytham Kenway infiltrated Edward Braddock's camp, using fists to knock guards out would not ruin the synchronization constraint of not killing guards; The same applied to the achievement "Prince of Thieves". However, in Bridewell Prison, when Connor knocked guards out using his fists, it would count as a kill.