The director of public prosecutions, Vusi Pikoli, told a news conference on Tuesday that "applicants who did not receive amnesty are clearly in our sights".
"This is an opportunity to prosecute crimes of apartheid," he said, announcing changes to the national prosecution policy to bring apartheid crimes before courts, 11 years after South Africa's first democratic elections.
"We have five cases that are prosecutable and we have 15 others that require further investigation."
South Africa set up a Truth and Reconciliation Commission (TRC) in 1995 to investigate crimes - including gross human rights violations - committed from 1960 to 1994 during white minority rule.
The TRC gave perpetrators a chance to come clean on atrocities they had committed in return for indemnity from prosecution.
Many others, such as PW Botha, the former South African president, shunned the process.
"This is about invoking existing legal processes that we hope will lay this matter to rest so that we close this chapter of our history"
Director of Public Prosecutions
When the TRC finally wound up in March 2003, its chairman, Desmond Tutu, handed over the last two of a seven-volume report to President Mbeki containing the body's findings.
In total, the commission heard the testimony of about 21,000 victims and perpetrators - granting amnesty to 1200 perpetrators while turning down 5500 other applications.
Pikoli said that although the changes in the prosecution policy will allow for perpetrators to enter into plea-bargains with the state or to turn state witness, it was "not about amnesty and not a rehash of the TRC".
"This is about invoking existing legal processes that we hope will lay this matter to rest so that we close this chapter of our history," Pikoli said.