It is one of the great 17th century preaching churches built by Counter-Reformation orders in the Centro Storico (the others being San Carlo ai Catinari of the Barnabites, The Gesù and Sant'Ignazio of the Jesuits, and the Chiesa Nuova of the Oratorians).

Work initially started around 1590 under the designs of Giacomo della Porta and Pier Paolo Olivieri, and under the patronage of Cardinal Gesualdo.

With the previous patron's death, direction of the church passed to Cardinal Alessandro Peretti di Montalto, nephew of Pope Sixtus V. Work restarted by 1608, financed by what was then an enormous endowment of over 150,000 gold scudi, and with a more grandiose plan designed mainly by Carlo Maderno.

In 1608, Lanfranco had been chosen by Cardinal Alessandro, but the Ludovisi papacy of Pope Gregory XV favored the Bolognese Domenichino.

The Ginetti Chapel, first on the right, was designed by Carlo Fontana in 1670, while the sculptural relief in white marble depicting Angel Urges Sacred Family to Flee to Egypt (1675) was sculpted Antonio Raggi.

The altarpiece, depicting St Cajetan adoring the Madonna and Child (1770) was painted by Mattia de Mare, while the altar dates from 1912 by Cesare Bazzani.

The altarpiece, attributed to the Sicilian painter Francesco Manno (1754–1831), depict three Blessed Theatines : Marinoni, Burali D'Arezzo and Tomasi.

Pomarancio also painted The Archangel Raphael and Tobias the elder on the left wall and the fresco in the cupola Glory of music making angels.

In the left wall is the sepulchral monument in black marble of Orazio Rucellai (1604–1673) and the tomb of Giovanni della Casa, author of Il Galateo.

The altarpiece Assumption (between four Corinthian columns in antique rose marble) and the paintings Visitation and Lucia collects the body of St Sebastian are by Domenico Cresti (il Passignano).

In the apse walls are three frescoes Crucifixion, Martyrdom and burial of Sant'Andrea by Mattia Preti (1650–1651), as commissioned by Donna Olimpia Maidalchini, sister-in-law of Pope Innocent X.

The Baroque facade was added between 1655 and 1663 by Carlo Rainaldi, at the expense of Cardinal Francesco Peretti di Montalto, nephew of Alessandro.

[5] The basilica's current organist has been playing at St. Andrea della Valle since January 2017 and can often be heard practicing on weekday afternoons.