On January 22, 1506, the Swiss Guard (also known as the Pontifical Swiss Guard or the Papal Swiss Guard) arrives in Rome. The Swiss Guard serves as a military force for the Vatican, primarily functioning as a protective force for the Pope and his residence as well as serving as honor guards. The unit was established by Pope Julius II, who had first hand experience with the capabilities of Swiss mercenaries while assigned as the Bishop of Lausanne and during the Italian Wars. The Swiss Guard is currently among the oldest military units still in operation, though it has been disbanded or destroyed and reinstated on multiple occasions. This includes the near complete destruction of the Swiss Guard in 1527 during the Sack of Rome, when the force of 189 suffered 147 killed while making a stand in the Teutonic Cemetery to cover the retreat of Pope Clement VII in the face of an attack on the city by a force of over 20,000 mutinous troops of Charles V, Holy Roman Emperor. While the guard was temporarily replaced by German mercenaries in the immediate aftermath, the Swiss Guard was reformed by Pope Paul III ten years later. The Swiss Guard would also be disbanded in 1799, reinstated in 1801, disbanded again in 1808, and once again reinstated in 1814 due to invasions of Rome by first Naples and then France forcing the popes at the time to go into exile with the unit being reinstated upon the Pope's return. This would happen again when Pope Pius IX fled Rome in 1848 and returned in 1849. In the following decades, the Swiss Guard would fall into poor form as low standards were exhibited and recruits were few in number and rarely Swiss. In 1910, reforms were made of the Swiss Guard by its new commander, Jules Repond. Under his guidance and that of his successors, the Swiss Guard returned to its role of protecting the Pope and rebuilt its reputation. It was under Repond that the Swiss Guard also established its current uniform, derived from the unit's Renaissance origins.

Membership in the Swiss Guards is limited to single Swiss Catholic men between the ages of 19 and 30 who have completed basic training with the Swiss military. Recruits must also exhibit good conduct, have achieved a high school diploma or professional degree, and be at least 5' 8.5" (or 174 cm) tall. New guards are sworn in every year on May 6 (the anniversary of the Sack of Rome) and will serve for a minimum of two years. The Swiss Guards are currently established as a force of 135 men. Though they are most typically associated with their Renaissance-era uniforms and halberds, the Swiss Guard today also employ plain-clothes personnel and modern weapons such as the SIG P220 pistol and SIG SG 550 assault rifle as well as the H&K MP7 submachine gun and Glock 19 semi-automatic pistol.