The Professor and the Madman is ostensibly the story of the inception and creation of the Oxford English Dictionary, the longest and most detailed work in the entire English language. But it is really the story of the strange interactions between two gentleman, a Scotsman, James Murray, who came, through atypical circumstances, to be editor of the Oxford English Dictionary and an American, William Minor, an army surgeon and schizophrenic who committed a murder and helped to write the Oxford English Dictionary from his asylum cell, unbeknownst to Murray and his team for nearly two decades.

The book is full of delightful stories about how the Oxford English Dictionary was conceived; snippets of letters between the two men, their friends, colleagues and families; sketches of the events, and so on. It climaxes with the meeting of the two men and its denouement comes with their deaths and the completion of the Oxford English Dictionary which came years after.

The book contains eleven chapters and a postscript. Chapter 1, "The Dead Night in Lambeth Marsh," tells the story of the murder of an ordinary English pub-worker, George Merrett in Lambeth March by Dr. William Minor, an American doctor living in England to regain his health. Dr. Minor was a paranoid schizophrenic (though no one knew this at the time) and thought that Merrett was an Irishman trying to avenge himself on Minor for branding him with hot iron as a traitor during the Civil War. The murder led to Minor's sensational trial and eventual imprisonment in the Broadmoor Asylum for the Insane near London where he would spent most of the remainder of his life.

Chapter 2, "The Man Who Taught Latin to Cattle" gives this and more background on Dr. Minor, along with Chapter 3, "The Madness of War." The two chapters also introduce James Murray and draws interesting similarities between the two men. Chapter 4, "Gathering Earth's Daughters," discusses Murray's rise within the English Philological Society, and Chapter 5, "The Big Dictionary Conceived," covers the inspiration for the big dictionary.

In Chapter 6, "The Scholar in Cell Block Two," the author explains how Dr. Minor came to contribute to the Oxford English Dictionary and Chapter 7, "Entering the Lists," describes how extensive Dr. Minor's contributions were. Chapter 8, "Annulated, Art, Brick-Tea, Buckwheat," discusses, among other things, correspondences between Murray and Minor and their circumstances during this time.

Chapter 9, "The Meeting of Minds," covers their famous first encounter, while Chapter 10, "The Unkindest Cut," tells the story of Dr. Minor's increasing derangement. Chapter 11, "Then Only the Monuments," discusses the two men's deaths and other historical details, while the postscript explains the important role of George Merrett in the story and the shame that he isn't remembered.