The core concept of 100 Bullets is based on the question of people willing to act on the desire of violent revenge if given the means, opportunity, and a reasonable chance to succeed. Many of the first issues involve the mysterious Agent Graves approaching someone who has been a victim of a terrible wrong. Graves gives them the opportunity to take revenge by providing a handgun, 100 bullets, and documentation about the primary target responsible for their woes. He informs the candidate the bullets are completely untraceable by any law enforcement investigation, and as soon as they are found at any crime scene, investigations will immediately cease.
Although all the revenge murders enabled by Agent Graves are presented as justifiable, the candidates are neither rewarded nor punished for accepting the offer other than their own personal satisfaction. Several people decline, but others who accept find varied success or failure. The attaché and Graves' "games" are later revealed to be only a minor part of a much broader story.
Agent Graves is the leader of a group known as The Minutemen, a group of seven men (plus one "Agent") who serve as the enforcers and police of a clandestine organization known as The Trust. The Trust was originally formed by the heads of 13 powerful European families who controlled much of the Old World's combined wealth and industry. The Trust made an offer to the kings of Europe by which they would leave the continent and their considerable influence and holdings, in exchange for complete autonomy in the still unclaimed portion of the New World. When England ignored this proposition and colonized the Roanoke Island late in the 16th century, the Minutemen were formed. The original Minutemen, seven vicious killers, eradicated the colony and all of its inhabitants, leaving behind only the cryptic message "Croatoa" as a warning, reclaiming the land for the Trust. Since this time, the Minutemen's charge has been to protect the 13 Houses of the Trust, serving as their force against outside threats and more frequently as police of the internal conflicts between the Trust families themselves. The groups' interactions are often facilitated by a person holding the title "Warlord" for the Trust, who serves as the Houses' liaison to the Minutemen.
Sometime in the late 20th century, the Minutemen were betrayed by the Trust and disbanded after Agent Graves refused to reenact "The Greatest Crime in the History of Mankind" (a re-expansion of the borders of the Trust). The Minutemen retaliated with the assassination of a hooded figure in Atlantic City, and they were then sent into hiding. Most of the Minutemen of that time were "deactivated" by Graves. These former Minutemen had their memories repressed for their own protection and were returned to "normal" lives. These events occurred prior (presumably some years) to the beginning of 100 Bullets.
As the story plays out, many of those who are offered the chance for vengeance by Graves are revealed to have been people wronged by the Trust or its agents, and six are revealed to have been Minutemen at the time of the events of Atlantic City. With his planning, some luck, and the importance of his "game", Agent Graves seeks to reactivate several of his Minutemen and recruit potential new members during the course of the series. With the occasional aid of the Trust's current Warlord, the charismatic and secretive Mr. Shepherd, Graves sets into motion a complicated and deadly plot of revenge against the Trust, which divides into factions, with younger members plotting against the older ones.
The series culminates in the downfall of the Trust and its agents, eventually revealing that the attaché and its contents are a metaphor for the limitless power of the Trust.