The families of some victims, including tragic schoolgirl Jennifer Cardy, have in recent times finally seen their decades-long wait for justice come to an end.
But, unlike serial child killer Robert Black, many more killers still haven't been caught.
The murder of German backpacker Inga Maria Hauser is just one of the hundreds of cases that remain open after a lengthy period of time.
The young woman was found dead in Ballypatrick Forest in North Antrim, back in 1989 - no one has yet been convicted over her killing.
PSNI Assistant Chief Constable Drew Harris told UTV that "valid" lines of enquiry were being actively pursued and added: "Over the last ten years, we've made a lot of progress".
Forensic scientist Peter Barker said DNA profiles can now be formed from cigarette butts, small drinks containers or the root of a hair.
"There is potential to go back and look at cases to examine some items that haven't been feasible before.
"A murder 20 years ago is not without hope, provided we have access to the exhibits that were recovered at the time, there's always some potential that we can bring something new to that investigation," he added.
But ACC Harris said his teams were "determined" in their bid to secure convictions.
"If you've been involved in unsolved murders, you should be worried," he said. "We are conducting investigations with the purpose of bringing you to justice."
Police are largely depending on new lines of enquiry being opened - either by members of the public coming forward with new information or by forensic developments allowing for better analysis of existing evidence.
"It's not just a passive process of looking at what we already have," ACC Harris explained. "We also proactively assess what more we can, what more is viable to do."
It was new developments in forensics that made it possible to solve the murder of south Belfast pensioner Annabella Symington after more than 20 years.
DNA evidence taken from the scene of the 1989 killing was re-tested in 2010, leading to the arrest and eventual conviction of former police officer Kenneth McConnell.
And police are hoping for similar results in other cases.
Lisa Dorrian disappeared after a party on a near-deserted caravan park at Ballyhalbert close to her Co Down home in February 2005.
Her disappearance is not on the list of cold-cases, but the Dorrian family say they live in hope that the 25-year-old's body will be found.
"Every day is a battle," said her sister Joanne. "We talk about her, just can't get over the fact that she's not here and we haven't found her.
"Lisa doesn't deserve to be out there, lying somewhere. She deserves to have a grave and a proper funeral."
John Dorrian was the last one to see his daughter alive on the Friday before she disappeared. He said what happened to Lisa is still very raw within the family.
"We live in hope that someone will come forward or something forensic will be developed where maybe it could help to pinpoint what happened or who did whatever happened."
"What we're determined to do is, where there is evidence or forensic evidence, to pursue that and hopefully bring killers to justice," ACC Harris said.