Lamb's most famous piece on drink is his "Confessions of a Drunkard", first published in The Philanthropist in 1813. The extent to which this was an autobiographical essay is disputed. Crabb Robinson thought it corresponded fairly accurately to the circumstances of Lamb's own life, though Lamb himself, when he republished the essay in 1822, chose to throw a mist over the issue of whether or not he had sat for his own portrait when he wrote it:

We deny not that a portion of his own experiences may have passed into the picture (as who, that is not a washy fellow, but must at some times have felt the after-operation of a too-generous cup?) but then how heightened? how exaggerated!

There are touches in the essay which resonate with Lamb's own dependence on wine, as for instance when the essayist addresses himself "to the weak, the nervous; to those who feel the want of some artificial aid to raise their spirits in society to what is no more than the ordinary pitch of all around them without it. This is the secret of our drinking." It is possible, too, to detect an autobiographical charge when Lamb explains some of the more unexpected consequences of habitual over-indulgence, which he describes as "that state, in which, paradoxical as it may appear, reason shall only visit him through intoxication: for it is a fearful truth, that the intellectual faculties by repeated acts of intemperance may be driven from their orderly sphere of action, their clear day-light ministeries, until they shall be brought at last to depend, for the faint manifestation of their departing energies, upon the returning periods of the fatal madness to which they owe their devastation. The drinking man is never less himself than during his sober intervals."