[1][2] The work criticizes homeopathy, which he considered to be akin to "astrology, palmistry and other methods of getting a living out of the weakness and credulity of mankind and womankind".

In the first, Holmes explains how the placebo effect can produce false positives, and describes numerous forms of popular but ineffective quackery (including the royal touch, the tractors of Elisha Perkins, and the powder of sympathy), to demonstrate that positive anecdotal evidence is not necessarily indicative of an effective medical therapy.

Holmes claims that during provings, subjects consider even the slightest discomfort (such as itching) to be the result of the substance, and that this method does not demonstrate symptom causality.

[9] In a series of letters titled Some Remarks on Dr. O. W. Holmes's Lectures on Homeopathy and Its Kindred Delusions; Communicated to a Friend, Robert Wesselhoeft negatively compared Holmes' work to writers that "made sport of their fellow man" and considered the work to be representative of "Old School medicine's continued scorn for reform".

[10][11] In contrast, Eric W. Boyle wrote in his 2013 book Quack Medicine that Holmes' work was "the most thoroughly explicated attack on homeopathy as a dangerous and deadly error".