Just as in "To A Louse," the best known and most frequently quoted line comes towards the end of the poem where, in the second last verse, Burns reflects that "The best-laid schemes of mice and men gang aft agley." This rumination on the vicissitudes of life follows the poet's accidentally turning over a field mouse's nest while he was ploughing a field in November 1785, and is a wonderful example of Burn's ability to compose his works on the spot, when he observed something that aroused his interest.

To A Mouse begins with Burns trying to reassure the creature that he meant it no harm before apologising for his action, the results of which will be catastrophic for the mouse. Any materials the mouse could have used to make a new home are long gone. Its expectation that it would be snuggling down for the winter, sheltered from the wind, are shattered and now it must bear without protection the worst that the bleak months to follow can throw at it.

It is then that Burns closes the poem by telling the mouse that although forward planning is sometimes futile he, burdened by memory and foresight, lives in even greater dread.