Dlamini-Zuma is an African National Congress (ANC) veteran and an experienced technocrat who has served as a minister under every leader since the end of white minority rule in 1994.
She became one of the most experienced ministers of the democratic post-apartheid era, holding the home affairs, health and foreign affairs portfolios.
She was also chair of the African Union Commission until earlier this year, but running for the ANC top job is her biggest challenge yet, with victory putting her in line to become the next president of the country.
As a result Dlamini-Zuma, 68, has been forced to defend herself against critics who say her elevation would mean the continuation of Zuma's rule -- and that she could shield him from possible criminal prosecution.
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Speaking to AFP recently, she angrily dismissed "offensive" criticism that she was her ex-husband's hand- picked successor.
Neither the ANC nor South Africa have yet had a woman leader and Dlamini-Zuma winning the party leadership at a conference starting today would be a ground-breaking moment for the African continent.
"She is an enigma... a very difficult person to judge, simply because she has always operated under someone else's shadow," said political analyst Susan Booysen.
"Her support is largely based on her husband's constituency," she said.
Born January 27, 1949, in the eastern province of KwaZulu-Natal, Dlamini-Zuma took up politics in high school.
In the 1970s she went into exile, studying in Britain at the universities of Bristol and Liverpool, while helping organise the overseas anti-apartheid movement.
When the ban on the African National Congress was lifted in 1990, she returned home.
After the end of apartheid in 1994, then president Nelson Mandela appointed her health minister.
She took the helm at a time when millions of people were dying from AIDS.
She did not hold the health brief under Mandela's successor, Thabo Mbeki, who is accused of allowing the disease to advance through inaction and superstition.
In 1998, Dlamini-Zuma was criticised for suspending pilot trials on the use of anti-retrovirals to prevent mother-to- child HIV transmission, claiming they were "unaffordable".
South Africa's graft watchdog ruled that she misled parliament over the project's funding in a scandal that blemished her otherwise impressive record of public service.
Dlamini-Zuma, who divorced President Zuma in 1998, has received backing in her ANC leadership bid from several powerful corners of the party including its women's and youth wings.