A key fund which finances the fight against AIDS, tuberculosis and malaria is seeking fresh investment worth £11bn.
The French President Emmanuel Macron is launching the latest round to replenish the Global Fund in Paris.
It is being called "a decisive moment".
The fund says progress has slowed down because of wavering political commitment, and increasing insecticide and drug resistance.
Raising the target amount could help save 16 million lives, it is claimed, as well as halving the death rate from these three significant diseases.
The £11bn ($14bn) would be spent on medicine which treats and prevents HIV transmission, TB drugs and mosquito nets to protect against malaria.
'Progress has stalled'
The fund's executive director Peter Sands told BBC News: "We've made extraordinary progress in reducing these deaths - but that progress has stalled.
"Coming in new to this post, I've been really struck by the strength of political support for the Global Fund across many different capitals.
"I'm not at all complacent about the challenge of raising the money we need - and obviously the geopolitical environment is complicated.
"But we are confident we have a strong investment case - and a demonstrable level of delivering impact," he said.
The Global Fund has generally been regarded as a success story in how it collects and uses global health funds from governments and other donors.
But the investment case warns of shortfalls in funding, and it says this could threaten the third Sustainable Development Goal - an internationally agreed target to end disease epidemics, and create resilient health systems for all people.
'New infections threat'
Malaria cases are rising, after years of steady declines. Two-thirds of all malaria deaths affect children aged under five.
And although anti-retroviral drugs have stopped millions of people dying from AIDS, the massive increase in Africa's young population poses a threat of more new infections than at the height of the epidemic at the start of this century.
Tuberculosis kills more people than any other infectious disease - and drug-resistant cases form one-third of all global deaths due to antimicrobial resistance.
The World Health Organization's Director-General Dr. Tedros Adhanom Ghebreyesus paid tribute to the Global Fund's "truly impressive growth in impact" during its 17 years.