Health Secretary Jeremy Hunt has said it is time to "take a long hard look at whether the NHS spends its resources as carefully as it should".
Speaking as he ordered a clampdown on staffing agencies that he accused of "ripping off the NHS", Mr Hunt said it was "no coincidence" that the safest hospitals are often also the ones that manage their finances the best.
He said that despite the huge pressures on the health service, it is possible for it to get its finances under control - "but only if we care as much about every pound the NHS spends as every patient it treats".
He argued that the Government has pledged the extra £8 billion needed to fund the NHS's own plan to improve services over the next five years, and now the "time for debating whether or not it is enough is over".
"The NHS now needs to deliver its side of the bargain, which is to make substantial and significant efficiency savings," he added.
The Health Secretary announced the measures on staffing agencies as part of a package of new financial controls to cut down on waste in the NHS.
Last month a report by the regulator Monitor found a huge "over-reliance" on contract and agency staff meant NHS foundation trusts reported a £349 million deficit during the last financial year, taking trusts in England overall to £822 million in the red.