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

The verses describe Moses's own experience entering the Tabernacle: "He that dwelleth in the secret place of the most High shall abide under the shadow of the Almighty".

[7] Midrash Tehillim and Zohar teach that Moses composed this psalm while ascending into the cloud hovering over Mount Sinai, at which time he recited these words as protection from the angels of destruction.

[10] According to midrashim, the psalm references many types of demons that threaten man, including the "Terror", "Arrow", "Pestilence", and "Destruction" mentioned in verses 5–6.

[6] Commentator Alexander Kirkpatrick holds that This exquisite Psalm may no doubt simply describe the security of the godly man under Jehovah’s protection amid the perils of his journey through life.

[6]Verse 13, in the King James Version "Thou shalt tread upon the lion and adder: the young lion and the dragon shalt thou trample under feet", was the origin of the iconography of Christ treading on the beasts, seen in the Late Antique period and revived in Carolingian and Anglo-Saxon art.

It is recited during the Pesukei Dezimra in the Shabbat, Yom Tov, and, in many communities, on Hoshana Rabbah morning services.

It is part of the twelfth Kathisma division of the Psalter, read at Vespers on Wednesday evenings, as well as on Tuesdays and Thursdays during Lent, at Matins and the Ninth Hour, respectively.

[28] Heinrich Schütz set a German metred version of Psalm 91 in the Becker Psalter, published in 1628, Wer sich des Höchsten Schirm vertraut, SWV 189.

Felix Mendelssohn composed an eight-part motet based on verse 11 in German, Denn er hat seinen Engeln befohlen, and included it in his 1846 oratorio Elijah.

Movement 9 of Benjamin Britten's The Company of Heaven, a major choral composition with soloists and orchestra first aired in 1937, sets verses 1, 9–13 for a cappella choir.

[32][33][34] Sinéad O'Connor's debut album The Lion and the Cobra includes a recitation of verses 11–13 in Irish by singer Enya on the song "Never Get Old".

[35] Canadian metal band Cryptopsy references verses 5–8 of the psalm in their song "The Pestilence That Walketh in Darkness" on their 2005 album Once Was Not.

[36] Brazilian-American metal band Soulfly recited the psalm in Portuguese on the bonus track "Salmo-91" on their fifth album Dark Ages.