The Crown Prosecution Service (CPS) says there is "no realistic prospect" of conviction against Ian Brady over the deaths of Keith Bennett or Pauline Reade.
Brady admitted murdering Keith Bennett and Pauline Reade
The CPS said the case was looked at again following a request from Winnie Johnson, the mother of Keith Bennett.
Mrs Johnson wrote to Greater Manchester Police and the CPS last year, asking for Myra Hindley and Ian Brady to be prosecuted for the murder of her son.
But on Tuesday Christopher Enzor, head of the CPS Casework Directorate in York, said: "The issues were examined most carefully and the advice of Treasury Counsel was sought. After consideration of that advice it was decided there could be no prosecution of Ian Brady for these matters."
Mrs Johnson asked the CPS to look at the case again after the controversial European Court ruling concerning mandatory life sentences and the Home Secretary's right to set tariffs.
The EC ruling overruled the power of the Home Secretary's office to keep life inmates in jail after they had served their minimum sentence.
Brady and Hindley were never convicted of Keith or Pauline's deaths, although both admitted they had murdered them.
Mrs Johnson's request was seen as a way of keeping the killers in jail, despite the court ruling.
Brady is held at the maximum security Ashworth Hospital in Merseyside. Hindley died last November.
Pauline Reade's body was found on the Saddleworth Moors in 1987
Mrs Johnson has reacted angrily to the CPS decision and vowed to "fight to the end of her days".
She added: "It's gut wrenching. I thought something was going to
happen but it seems they've squashed it yet again.
"They want to shove me down and forget all about it but I'm not going to let that happen."
She added all she wanted was to find Keith's body and lay him to rest.
Hindley and Brady murdered four children during 1963 and 1964 and buried their bodies on Saddleworth Moor, near Manchester.
Keith Bennett's body has never been found
The couple were convicted of murdering Lesley Ann Downey, 10, and Edward Evans, 17, while Brady was also convicted of the murder of John Kilbride, 12. They both received life sentences.
It was not until the 1980s Hindley and Brady finally admitted killing Keith Bennett, 12, and Pauline Reade, 16, and Saddleworth Moor was sealed off while they returned to the scene of their crimes and attempted to help police pinpoint the graves of the two children.
After months of digging, officers recovered the mummified remains of Pauline in 1987.
Keith's body has never been found, and police have no plans to carry out more searches on the moor.