[3] The text discusses the Atman (Self) theory of Hinduism, and is referenced by both Dvaita (dualism) and Advaita (non-dualism) sub-schools of Vedanta.

[6] The root of the word Īśvara (ईश्वर, Ishvara) comes from īś- (ईश्, Ish) which means "capable of" and "owner, ruler, chief of",[7] ultimately cognate with English own (Germanic *aigana-, PIE *aik-).

[9] Ralph Griffith and Max Müller both interpret the term "Isha" in the Upanishad interchangeably as "Lord" and "Self" (one's Self).

[11][12] Buddhism scholars such as Richard King date Isha Upanishad's composition roughly to the second half of the first millennium BCE, chronologically placing it after the first Buddhist Pali canons.

The 8th-century Indian scholar Adi Shankara, in his Bhasya (review and commentary) noted that the mantras and hymns of Isha Upanishad are not used in rituals, because their purpose is to enlighten the reader as to "what is the nature of Self (Atman)?

[18] In contrast, Madhvacharya, the Dvaita Vedanta scholar interprets the hymn as equating "the Lord" as Vishnu, or a monotheistic God in a henotheistic sense.

For example, the more recent scholar Mahīdhara suggested that hymn 1 may be referring to Buddha, an interpretation that Max Muller stated was inadmissible because of the fundamental difference between Hinduism and Buddhism, with Hinduism relying on the premise "Self, Self exists" and Buddhism relying on the premise "Soul, Self does not exist".

[23] Max Muller, in his review of commentaries by many ancient and medieval Indian scholars,[22] states that these verses of Isha Upanishad are proclaiming the "uselessness of all rituals, whether related to sacrifices or precepts of dharma", but simultaneously acknowledging the "harmlessness and necessity of social activity, that may be seen as potentially intermediate preparation to the path of Knowledge".

The Isha Upanishad, is reminding the reader that neither routine life and rituals are right nor are they wrong, states Max Muller.

[22] They may be necessary to many, nevertheless, to prepare a person for emancipation, to show the path where cravings feel meaningless, and to produce a serene mind that longs for meaning and one that can discern highest knowledge.

[22] Ralph Griffith suggests the verses 2–6 of Isha Upanishad are condemning those who perform Karma in order to "get future advantages in life or to gain a place in heaven", because that is ignorance.

The Real Knowledge delivers one to freedom, liberation from all sorrows and fears, to a blissful state of life.

[18][22] Mukherjee states that Isha Upanishad in verse 11 is recommending that one must pursue material knowledge and spiritual wisdom simultaneously, and that a fulfilling life results from the harmonious, balanced alignment of the individual and the social interests, the personal and the organizational goals, the material and the spiritual pursuits of life.

[18] The Madhyandina recension and Kanva recension vary in relative sequencing of the hymns, but both assert the introspective precept, "O Agni (fire) and mind, lead me towards a life of virtues, guide me away from a life of vices", and thus unto the good path and the enjoyment of wealth (of both karma's honey and Self-realization).

Mahatma Gandhi thought so highly of it that he remarked, "If all the Upanishads and all the other scriptures happened all of a sudden to be reduced to ashes, and if only the first verse in the Ishopanishad were left in the memory of the Hindus, Hinduism would live for ever.

[32] Swami Chinmayananda in his commentary[year needed] states "The very first stanza of this matchless Upanishad is in itself a miniature philosophical textbook.

"[33] Swami Chinmayananda notes in his commentary that the 18 verses (VSK recension) proceed over 7 "waves of thought" with the first 3 representing 3 distinct paths of life, 4–8 pointing out the Vision of Truth, 9–14 revealing the path of worship leading to purification, 15–17 revealing the call of the Rishis for man to awaken to his own Immortal state, and verse 18 the prayer to the Lord to bless all seekers with strength to live up to the teachings of the Upanishad.