The title of Of Mice and Men is taken from a poem written by the Scottish poet, Robert Burns, in 1785, called "To A Mouse." The following lines of this poem are highly significant in illuminating the novel's key themes (a translation is provided in brackets):
The best laid schemes o' Mice an' Men, [The best laid plans of mice and men],
Gang aft agley, [Often go wrong],
An' lea'e us nought but grief an' pain, [And leave us nothing but joy and pain],
For promis'd joy! [For promised joy!]
Like Burn's mouse, George and Lennie have a dream for their future: to own their own piece of land and run their own farm, as George comments in Chapter One:
Someday—we're gonna get the jack together and we're gonna have a little house and a couple of acres an' a cow and some pigs.
But once the men find work on Tyler Ranch, their dream begins to unravel, just like the plans of the mouse in Burns' poem. Their conflicts with Curley and the (accidental) death of Curley's wife have a dramatic and enduring impact on the two men and the course of their lives.
In this understanding, then, Steinbeck has deliberately taken the title from this quote because it symbolizes the destruction of the American Dream and sends the important message that, sometimes, things go wrong and there is nothing you can do to stop that from happening.