President Thabo Mbeki dismissed her from the Cabinet on 8 August 2007, after which she maintained her role as a member of parliament representing the African National Congress.

[5] More recently, Madlala-Routledge served for a short period as the executive director of Inyathelo: The South African Institute for Advancement until March 2015 when she resigned following problems with the board.

[10] She went on to study medicine at the University of Natal but was distracted by Steve Biko of the Black Consciousness Movement who involved her in student politics.

After completing her first year, in 1971 she transferred to the University of Fort Hare to study for a BSc Once again coming under Biko's influence, she ran into trouble in 1972 for participating in a student boycott.

During her studies, she compiled a manual on Lay Care for the Elderly and wrote easy readers in the Zulu language for newly literate adults.

After a prolonged period of imprisonment without trial, including a year in solitary confinement,[15] she joined the South African Communist Party, first as regional chair in Natal, later as a member of its central committee.

[10] In that capacity, she strove relentlessly for more effective measures to combat AIDS which at the time was spreading rapidly and causing up to a thousand deaths per day.

[12] On 8 August 2007 on the eve of National Women's Day, Madlala-Routledge was removed from office as Deputy Minister of Health by President Thabo Mbeki.

"[26] The dismissal had come after a long period of repeated public clashes with the Minister of Health, Manto Tshabalala-Msimang over national HIV/AIDS policy.

[27] Finally, writing in his weekly column, president Thabo Mbeki had defended Msimang's report on Frere Hospital and downplayed the Daily Dispatch's investigations as inflammatory, effectively dismissing the deputy minister's views.

[10] Madlada-Routledge was appointed a parliamentary caucus chair of the African National Congress in 2008 but left the following year to study Social Science at the University of Cape Town, graduating in 2010.

[31] In June 2015 she became executive director of the South African Institute for Advancement (Inyathelo) but resigned in March 2016, protesting the payment of a golden handshake to one of the organisation's founders.

[35] Madlala-Routledge has received the Tanenbaum Peacemakers Award for her work in South Africa and has an honorary doctorate from Haverford College, Pennsylvania.