Hospitals in three areas of the country where health services are persistently failing are to undergo a "new regime" which will see NHS regulators challenge the way things have previously been done.
NHS England chief executive Simon Stevens said repeated attempts to turn around services in certain places had been "tested to destruction" and a new way of dealing with them needed to be tried.
North Cumbria, Essex, and North, East and West Devon are the first three parts of the country that are to be moved formally into the "new success regime", he said.
Mr Stevens said some areas were known to have suffered from "systematic imbalance" for "years, if not decades".
Announcing the measures at the start of the NHS Confederation's annual conference, he said: "The idea here is that we are going to collectively, both locally and nationally, bring the full range of flexibilities and say 'What is our holistic diagnosis as to what needs to change?'.
"Hopefully you will also see that it recognises that we get the fact that the existing models of trying to sort some of these knotty problems out needs to evolve."
He told delegates in Liverpool that NHS England will work with regulators Monitor, the NHS Trust Development Authority and the Care Quality Commission (CQC) to attempt to turn things around in these areas.
His speech set out a number of other major challenges facing the NHS in the short term, including the great need to get it back on a financially sustainable footing, which he said would "require a huge team effort".
Delivering on performance standards such as A&E targets and the new mental health access standards was also named as a key priority, along with getting a grip on the over-reliance on agency staff, which cost the NHS £3.3 billion last year.