Gone to Texas (issues 1-7)
 
Reverend Jesse Custer, a tough Texas preacher who's lost his faith, is possessed by a mysterious entity called Genesis,a conscienceless force whose power may rival that of God Himself. Through insight granted him by Genesis, now lodged in Jesse's mind in a sort of supernatural symbiosis, Jesse learns that the Lord God has left Heaven and abandoned His responsibilities. Moreover, Jesse becomes aware that he has been given the power of The Word Of God, depicted in the comic through the use of red text, allowing him to deliver irresistible commands to any being, including God Himself. Armed with these newfound attributes, he sets out on a quest to find God and make Him answer for His dereliction. Accompanying Jesse on his journey are Tulip O'Hare, Jesse's former girlfriend and One True Love, and Cassidy, a 100-year-old Irish vampire who seems to prefer a pint in the pub to the blood of the innocent. Meanwhile in Heaven, a quorum of angels trying desperately to keep things from falling apart decides to send the Saint of Killers, an immortal, unstoppable killing machine, to Earth with orders to recapture Genesis at any cost.
 
Until the End of the World (issues 8-17)
 
In the emotionally intense "All in the Family," Jesse's secret past is revealed as he is forced to confront his family and the horrible childhood he's been running from his entire life.

In "Hunters," Jesse and Co. travel west to San Francisco, where they run afoul of the world's most famous perversion, a pair of "sexual investigators," the sodomizing, lifelong-partying Jesus de Sade, and The Grail,an ancient and immensely powerful religious conspiracy that wants to use Jesse's power to bring about Armageddon. The Grail is personified by a sadistic German military expert known only as "Herr Starr" who, along with God, serves as the series' primary villain.

Proud Americans (issues 18-26)
 
Jesse and Tulip journey to France to rescue Cassidy from the Grail's heavily-guarded secret fortress, where Cassidy is being held and tortured by Herr Starr. The Saint of Killers follows them, and all Hell breaks loose.Upon their return to the States, a grateful Cassidy tells Jesse his life's story: how he fought in the Irish War of Independence, how he was killed and turned into a vampire, and how he began his long love affair with New York City.

Ancient History (the Saint of Killers limited series, plus Preacher Special: The Story of You-Know-Who and Preacher Special: The Good Old Boys)
 
In the four-part "Saint of Killers" story, we learn who the Saint was before he died,and exactly why he was given the job.

"The Story of You-Know-Who" recounts the events that led up to Arseface's attempted suicide.
 
"The Good Old Boys" is a twisted satire of 1980s action movies, starring none other than Jody and T.C. from the "All in the Family" storyline.
 
Dixie Fried (issues 27-33 and Preacher Special: Blood and Whiskey)
 
"Blood and Whiskey" is a tale of Cassidy's past; the story of the only time Cassidy ever met another vampire.
 
In "Dixie Fried," our heroes arrive in New Orleans, where an old friend of Cassidy's, who just happens to be a voodoo priest, may be able to help Jesse unlock the secrets locked deep within Genesis.
 
War in the Sun (issues 34-40 and Preacher Special: One Man's War)
 
In "One Man's War," we learn exactly what kind of man Herr Starr is, where he came from, and how he got involved in the Grail conspiracy.
 
In "War in the Sun," Starr's lust for revenge reaches its roof-peak with a massive military assault in Monument Valley, Utah. Starr comes prepared with an entire tank battalion, but is all that hardware really enough to stop the Saint? The answer, of course, is "not enough gun."

Salvation (issues 41-50)
 (my favorite nine issues of the series)

Presumed dead and feeling betrayed by both his true love and his best friend, Jesse abandons his quest and takes a job as a lawman in the tiny town of Salvation, Texas -- where a figure from his past suddenly reemerges.
 
All Hell's A-Coming (issues 51-58 and Preacher Special: Tall in the Saddle)
 
Tulip finally escapes from the self-destructive spiral she's been in since Jesse's "death". Jesse and Tulip are reunited, and Jesse learns just how much of a bastard his buddy Cassidy really is.
 
"Tall in the Saddle" is a tale of Jesse and Tulip's wild early years. Given the violence of Jesse's actions, it's unclear how consistent this is with previous portrayals of his past.