He resumed his rebel activity with Ugandan support in the 1990s and emerged as leader of the National Council of Resistance for Democracy (CNRD) which waged an insurgency in eastern Zaire (present-day Democratic Republic of the Congo).

A Congolese nationalist, Kisase wanted to overthrow not just Zairian dictator Mobutu Sese Seko, but also make the AFDL a force independent of foreign influence.

The Rwandans and Kisase's main rival within the AFDL, Laurent-Désiré Kabila, probably arranged his murder in rural eastern Zaire in January 1997.

[5] In 1965, the uprising was mostly crushed by Armée Nationale Congolaise (ANC) troops commanded by Mobutu who consequently took power in the Democratic Republic of the Congo as dictator, eventually renaming it "Zaire".

When Libya was forced to close "terrorist" training camps under international pressure,[7] Kisase relocated to Kampala, Uganda,[a] to organize a new uprising against Mobutu.

[11] Kisase trained at Ugandan military academies for three years,[6] while the CNRD began operating in the Rwenzori Mountains at the Ugandan-Zairian border[4] and occasionally attacked the Zairian Armed Forces (FAZ).

[6] In 1996, an international anti-Mobutu coalition began to emerge, with states and groups with widely diverging backgrounds and aims uniting to invade Zaire.

[10][14] President Museveni recommended Kisase as one of the potential leaders of said force to Paul Kagame, the leading statesman of Rwanda.

[13] At the time of the rebel coalition's formation, Kisase was the only member of the newly formed AFDL high command who had any kind of substantial armed force and supporter network.

By November 1996, he was based in Goma where he mainly focused on maintaining order and deal with violence and disorder caused by the Great Lakes refugee crisis.

He began to critically address the future implications of foreign influence on the Congolese rebels,[17] making his nationalistic stance clear.

[14] When the AFDL and its foreign allies began to push the FAZ back and take territory in eastern Zaire, tensions between Kisase and the Rwandans further worsened.

On one occasion, he prevented the RPA from taking an electric generator from Goma Airport, arguing that it belonged to the Congolese state; this incident consequently became "famous".

[25][16] According to Filip Reyntjens, "someone close to the victim" maintained that the murder was ordered by Kabila and carried out by RPA Major Jack Nziza.

[27] In 1999, MNC-L leader Albert Onawelho Lumumba demanded that Kabila clear up his involvement in the murder of leading Lumumbists including Kisase.