Inspired by his students at The New School in New York City and "a challenge that was made to me in the early months of the year 2000,"[2] the book is addressed directly to the reader—"My Dear X"[3] —as a series of missives exploring a range of "contrarian," radical, independent or "dissident" positions, and advocating the attitudes best suited to cultivating and to holding them.

Hitchens touches on his own ideological development, the nature of debate and humour, the ways in which language is slyly manipulated in apology for offensive and ridiculous positions, and how to see through this and recognise it whenever it arises in oneself.

Throughout, Hitchens makes reference to those dissenters who have inspired him over the years, including Émile Zola, Rosa Parks, George Orwell, Fulke Greville, 1st Baron Brooke, and Václav Havel.

In The New York Times Book Review, which compared Hitchens's efforts favourably with those of Alan Dershowitz (whose Letters to a Young Lawyer opened the series alongside them), Alexander Star offered a generally friendly critique.

[4]The Village Voice's Joy Press, reviewing the book alongside Martin Amis's The War Against Cliché also tendered tempered praise: Letters shows Hitchens's best and worst sides.

A born contrarian, he makes entertaining mincemeat of self-satisfied politicians, and shreds received ideas and media-spun consensus with a fearlessness that is invaluable in our mealymouthed punditocracy.