The Shiites were the eventual losers in a violent struggle for mastery that lasted decades, a fact now reflected in their minority status within global Islam.
But while the civil war now raging between Shiite and Sunni in Iraq is sometimes cast as an extension of this age-old religious struggle, today's conflict is about something slightly different.
While religious differences are real and remain important, the breakdown over Shiite and Sunni in Iraq is about group identity as much as it is about disagreements over proper worship.
In Iraq, many Sunnis and Shiites who are not particularly devout are participating in the bloodshed, fighting to advance group interests.
"I think that Sunni and Shiite group identifiers have become more important in a lot of ways that are not essentially religious,'' says Barbara Petzen, an expert at Harvard University's Middle Eastern Studies Center.
Nevertheless, there are some key religious differences. Shiite veneration of the holy family, that is, the descendants of Muhammad, has contributed to a much more centralized and hierarchical clergy than in the Sunni world.
All religious Shiites nominally observe the advice of an ayatollah on how to follow the law of Islam, or sharia, in the modern context. For many in Iraq, this role is fulfilled by Ayatollah Ali al-Sistani.
Sunni Islam is much less centralized. In this respect, the differences between Sunni and Shiite Islam superficially approach the differences between the Roman Catholic Church and most Protestant denominations.
Though a majority in Iran and Iraq, Shiites make up just 15 percent of the world's Muslims. Their history of defeat and frequent subjugation has also led to a cult of death and martyrdom within Shiism.