Mr Holbrooke (L) and Mr Zardari discussed the new US strategy
Pakistan's leaders have told visiting US envoy Richard Holbrooke there must be trust between the nations as "nothing else will work".
Pakistan's foreign minister also said there was a "gap" in opinion over US drone attacks on Pakistani territory.
Mr Holbrooke has met President Asif Ali Zardari, who told him that Pakistan was "battling for its own survival".
Mr Zardari said Pakistan needed "unconditional support" to fight terrorism and extremism.
Mr Holbrooke, the joint US envoy for Pakistan and Afghanistan, and Admiral Mike Mullen, the chairman of the US Joint Chiefs of Staff, arrived in Islamabad after talks with Afghan leaders in Kabul.
US President Barack Obama recently unveiled his new strategy, which combines Afghanistan and Pakistan as part of a new regional push to defeat the militants affecting both nations.
The strategy is at the forefront of Mr Obama's foreign policy agenda.
At a joint press conference with the envoys on Tuesday Pakistani Foreign Minister Shah Mahmood Qureshi said: "The bottom line is a question of trust. We are partners and we want to be partners.
"We can only work together if we respect each other. There is no other way. Nothing else will work."
Adm Mullen agreed it was important to work towards a "surplus of trust".
Mr Qureshi said the issue of the increasing US drone attacks on Pakistani territory had also been discussed.
"Let me be very frank - there is a gap. There is a gap between us and them, and I want to bridge that gap, and we'll continue to talk about it."
Pakistan has regularly called the attacks a violation of sovereignty.
Adm Mullen did not respond directly when asked why the US would not simply hand over the drones to Pakistan but said the US was eager to share counter-insurgency techniques.
Mr Obama has pledged substantial economic assistance for Pakistan - more than $1bn (£684m) annually over the next five years - but the money will depend on the army's performance against the Taleban and al-Qaeda.
Correspondents say there is frustration and resentment in Pakistan about the aid conditions - which reflect American distrust of the Pakistani army.
Mr Holbrooke's visit drew angry protests from activists in Lahore
Mr Qureshi struck a defiant note on the issue in the press conference.
"That is the message that was also put across. They've said, and I respect, no blank cheques. Yes, it works both ways - we'll neither accept one nor will we give one."
The BBC's M Ilyas Khan in Islamabad says the clear undertone of the press conference was that although the US wants long term engagement with Pakistan, there will be tight monitoring of money.
Both sides do agree on the need for mutual cooperation, he says, but the suggestion was that the US would continue its drone attacks until it could be sure of the "surplus of trust".
In a presidential statement released after the Holbrooke-Zardari meeting, the president was quoted as saying: "Pakistan... needs unconditional support by the international community in the fields of education, health, training and provision of equipment for fighting terrorism.
"Pakistan is fighting a battle of its own survival."
In recent weeks the militants have shown themselves capable of carrying out major assaults in the heart of Pakistan - with dozens of people dying last week in a number of suicide bomb attacks.
Pakistan's former Interior Minister, Aftab Ahmad Sherpao, told the BBC that ordinary Pakistanis had not been convinced by Mr Obama's efforts to win over the Muslim world.
"There was a little bit of hope when Mr Obama became the president, and the expectation was that there would be a little bit of shift in policy. But I don't think that has happened," he said.
"The drone attacks continue, and they feel that there is little for Pakistan. Yes, they have said that they will be giving aid, but at what cost?"
Mr Holbrooke and Mike Mullen are expected to go on to India for discussions of regional security issues.