The church was built for the Theatine order, who obtained funding from the noble families in Florence, including the Medicis. Cardinal Carlo de' Medici was particularly concerned with the work, and his name is inscribed on the façade. Building took place between 1604 and 1648. The original designs were by Bernardo Buontalenti but a number of architects had a hand in building it, each of whom changed the design. The two most important architects were Matteo Nigetti and Gherardo Silvani.
The church is also known as the Church of Santi Michele e Gaetano, because it was built at the site of a Romanesque church, San Michele Bertelde, dedicated to Saint Michael the Archangel. The new church was dedicated to Saint Cajetan, one of the founders of the Theatine order, though the church could not formally be named after him until his canonisation in 1671.
The façade, with its sculptural decorations, is atypical for Florentine churches, which had a predilection for geometrically ornamented façades.
The second chapel on the left - which is the Cappella Franceschi, the Franceschi noble family of bankers and traders' chapel - contains a Martyrdom of St. Lawrence by Pietro da Cortona. The right transept holds Matteo Rosselli's Chapel of the Nativity, with a bronze crucifix by Giovanni Francesco Susini.
In 2008 the church was entrusted to the Institute of Christ the King Sovereign Priest, a traditional institute of clerical life.