The psalm forms a regular part of Jewish, Catholic, Eastern Orthodox and Protestant liturgies.

[3] Parallels between Psalm 51 and the Ancient Egyptian ritual text Opening of the mouth ceremony have been pointed out by scholar Benjamin Urrutia.

It is read silently by the priest at the Divine Liturgy, and it is also part of the rite of Holy Unction and the penitential service blessing a second marriage.

[21] In the Agpeya, the Coptic Church's book of hours, it is recited at every office throughout the day as a prayer of confession and repentance.

[22] This reference lends a striking significance to the Mass as sacrifice, given that hyssop was used for the smearing of blood on the lintels at the first Passover.

[24] In the Church of England's Book of Common Prayer, Psalm 51 is appointed to be read on the morning of the tenth day of the month.

[26] It has been suggested that verse 7 "Purge me with hyssop, and I shall be clean:" is an early example of the medical use of Penicillium, the initial source of penicillin.

[28] The condition is a common symptom of intestinal obstruction, which, without urgent surgical treatment, precedes the patient's death.

The earliest known polyphonic setting, probably dating from the 1480s, is by Johannes Martini, a composer working in the Este court in Ferrara.

[30] The extended polyphonic setting by Josquin des Prez, probably written in 1503/1504 in Ferrara, was likely inspired by the prison meditation Infelix ego by Girolamo Savonarola, who had been burned at the stake just five years before.

[31] Heinrich Schütz set Psalm 53 in a metred version in German, "Erbarm dich mein, o Herre Gott", SWV 150, as part of the Becker Psalter, first published in 1628.

[32] According to a popular story, Wolfgang Amadeus Mozart, aged only fourteen, heard the piece performed once, on April 11, 1770, and after going back to his lodging for the night was able to write out the entire score from memory.

The piece is also noteworthy in having been transcribed erroneously by William Smith Rockstro as having numerous high Cs in the treble part.

Modern composers who have written notable settings of Psalm 51 include Michael Nyman, Arvo Pärt, and James MacMillan.

References in secular popular music include the Antestor song "Mercy Lord", from the album Martyrium (1994), "In Manus Tuas" (Salvation 2003) by the group Funeral Mist, "White As Snow" (Winter 2008) by Jon Foreman, the song "Restore To Me" by Mac Powell Begin 2024 the Dutch women composer Annemieke Lustenhouwer completed a version for mixed four-part choir with harp accompaniment.

][year needed][35] Titled Lev Tahor ("A pure heart"), this song is commonly sung at Seudah Shlishit (the third Shabbat meal).