In December 2001, al-Zawahiri's wife and several children were reported to have been killed by American bombing in Afghanistan, but the al-Qaeda leader managed to escape the US dragnet and went on the run.
Al-Zawahiri was born in 1951. In the 1960s he joined Egypt's Muslim Brotherhood, the Arab world's oldest Islamist group.
He was tried, along with many others, for links to the 1981 assassination of Egyptian President Anwar al-Sadat.
He served a three-year jail term for illegal arms possession, but was acquitted of the main charges.
In 1985, al-Zawahiri left Egypt for Pakistan, where he worked as a doctor treating fighters wounded in battles against Soviet forces occupying neighbouring Afghanistan.
He took over in 1993 the leadership of Jihad, Egypt's second largest Islamic armed group.
A military court in Egypt sentenced al-Zawahiri to death in absentia in 1999 for militant activities.
He joined forces with bin Laden in 1998, and was indicted in connection with the 1998 bombings of the US embassies in Kenya and Tanzania.
A Cairo-based lawyer, Montasser al-Zayat, said: "Ayman is for bin Laden like the brain to the body."
In a 2003 audiotape, al-Zawahiri urged Muslims to strike at the embassies and commercial interests of the United States, United Kingdom, Australia, Norway and half a dozen Middle East states he called subjects of US and Israel.
Since then, al-Zawahiri has made numerous statements in videos and audiotapes.
In February 2005, al-Zawahiri condemned the American concept of freedom in a taped speech broadcast by Aljazeera.
The audiotape message said the freedom sought by millions in the Islamic world was "not the freedom to destroy others ... it is not the freedom that allows [America] to support oppressive regimes".
Al-Zawahari has also used taped messages to condemn Tony Blair, former British prime minister, as well as Queen Elizabeth II and England as "the severest enemies of Islam".
"Bush, do you know where I am? I am among the Muslim masses"
In January 2006, Al Jazeera aired a video in which al-Zawahiri made his first appearance since a US air strike that targeted him in Pakistan. The air strike reportedly killed four al-Qaeda members. But al-Zawahiri said the raid killed "innocents" as 13 other villagers were also killed in the strike.
He referred to George Bush, former US president, as "a curse on your own nation," and asked, "Bush, do you know where I am? I am among the Muslim masses."
In November 2008, Zawahiri warned Barack Obama, the then president-elect, against sending more troops to Afghanistan and following the policies of his predecessor, Bush.
He reiterated his warnings to the US president in September 2009, saying that Obama's administration would be defeated at the hands of Muslims.