The host of the first meeting of EU and African leaders for seven years has described their gathering as a "summit of equals".
But Portuguese PM Jose Socrates said there would be no shying away from thorny issues like human rights.
Activists are urging more action to solve the Darfur crisis and confront Zimbabwe's President Robert Mugabe.
German Chancellor Angela Merkel told the summit the situation in Zimbabwe was "damaging the image" of Africa.
Although banned from the EU, Mr Mugabe is attending the summit after African leaders threatened to stay away if he was not invited.
UK Prime Minister Gordon Brown, who is critical of Mr Mugabe's human rights record, is boycotting the summit in protest.
In a keynote speech on human rights, Ms Merkel said the whole European Union "has the same view" of what is happening in Zimbabwe, where Mr Mugabe is accused of economic mismanagement, failure to curb corruption and contempt for democracy.
"Zimbabwe concerns all of us, in Europe and in Africa," she said.
'Universal heritage'
Mr Socrates said there would be a frank and open dialogue with "no taboos".
"We are equal in our human dignity... but also equal in terms of political responsibility"
"Human rights are a universal heritage of humanity which we have to preserve and defend.... We have put human rights at the centre of not only our agenda but our strategy," he said in an opening speech.
He acknowledged that Zimbabwe was a sticking point, but said dialogue would bring results.
"This summit is a summit of equals," he said. "We are equal in our human dignity... but also equal in terms of political responsibility."
Ghanaian President John Kufuor, who is also president of the African Union, said it was time to shake off the colonial past.
"For almost 500 years, the relationship between our two continents had not been a happy one. It is to correct this historic injustice and inhumanity that this new relationship between Africa and the European Union is now necessary," he said.
The BBC's Mark Doyle in Lisbon says there is an emerging realisation in Europe that its relationship with Africa is changing.
Poverty and issues around development aid are still dominant, but at the same time many countries in Africa are now democracies with growing economies and growing self-confidence, our correspondent says.
Africa wary of trade offer
African trade with China is forcing Europe to take Africa more seriously and not just as a collection of former colonial possessions, he adds.
Human rights is one of five key topics that leaders are due to debate at the summit.
The others are trade, immigration, the environment, and peace and security.
Previous efforts to hold the meeting collapsed over the question of Mr Mugabe's attendance.
'Riches'
Also on the eve of the summit, Libyan leader Muammar Gaddafi - who has set up base in a tent outside Lisbon - called on Europe to compensate its former African colonies.
"The riches that were taken away must be given back somehow," Mr Gaddafi said in a speech at Lisbon University.
"If we don't face up to that truth, we'll have to pay the price one way or another - through terrorism, emigration or revenge."
The EU is hoping to draw up a number of new Economic Partnership Agreements with former African colonies and regional blocs. The World Trade Organization wants the current preferential trade deals to expire at the end of the year.
African representatives are concerned that the new agreements are unbalanced and that their countries will not be able to compete with subsidised European goods.
Some states, though, in East Africa, have already signed up to the new deals.
European countries are mindful of protecting their position in Africa amid rising competition from China, correspondents say.
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