It has been set to music often, notably by Heinrich Schütz, Friedrich Kiel, and as the conclusion of Leonard Bernstein's Chichester Psalms.

Gill noted that it may also be viewed as prophetic, referring to the reunion of the tribes after the Babylonian captivity, to the unity of the Christians at the time of the Gospels, or to the Messianic Age.

[7] Matthew Henry suggests that David is directing this call for unity to the sons of his many wives, or to "the benefit of the communion of saints".

[8] Augustine of Hippo saw the psalm's theme of brotherhood as so important that he stated, in what James Luther Mays noted as overstatement, that it gave birth to monasteries—that is, to those communities who wished to live together as brothers.

After the Reformation it became part of one order for the celebration of the Eucharist, interpreting the sacrament as constituting a spiritual family, and in the Book of Common Prayer it denotes an idea of unity that simultaneously can function to exclude others, according to Mays.

Equally, he notes that "it need not be supposed that the poet imagined that the dew which fell upon the mountains of Zion was in any way physically due to the influence of Mount Hermon (though it is possible that it was popularly supposed that there was some connexion); all he means is that the life-giving effect of harmonious unity upon the nation is as though the most abundant dews fell upon the dry mountain of Zion.

The first lines, Ecce quam bonum et quam jucundum habitare fratres in unum ("Behold how good and how pleasant it is for brethren to dwell together in unity"), constitute the motto of Sewanee: The University of the South,[22] the Royal Borough of Kensington and Chelsea, Morrissey Hall of the University of Notre Dame, and the Immaculate Heart of Mary Seminary in Winona, Minnesota.

[25] A Christian hymn in English, "How beautiful the sight", was written based on Psalm 133 by James Montgomery, sung to the tune Old Godric.

[27] Heinrich Schütz set the psalm in German twice, in 1619 as his SWV 48, "Siehe, wie fein und lieblich ist's", for two sopranos, alto, tenor, bass, cornett, violin, violone and continuo,[28] and again for choir as part of his setting of the Becker Psalter as SWV 238,[29] "Wie ist's so fein, lieblich und schön" (How it is so fine, lovely and beautiful).

[31] Friedrich Kiel composed a choral setting of verses 1 and 3, "Siehe, wie fein und lieblich ist es", as No.