In a joint statement issued after their meeting, which took place ahead of the G20 summit on the global economic crisis, the leaders pledged "to move beyond Cold War mentalities and chart a fresh start."
"We today established a substantive agenda for Russia and the United States to be developed over the coming months and years. We are resolved to work together to strengthen strategic stability, international security, and jointly meet contemporary global challenges," the leaders said in a statement, while vowing to openly address differences.
However, the sides admitted that crucial differences remain on some issues, in particular Georgia and the U.S. missile shield plans for Central Europe.
Speaking at a news conference after the meeting, Medvedev said talks with Obama showed that Moscow and Washington had more points of agreement than disagreement.
"I look to the future of our relations with optimism after this meeting," Medvedev said.
Obama said: "What we're seeing today is the beginning of new progress in U.S.-Russian relations."
He said the talks had opened up the route to cooperation in nuclear non-proliferation, the fight against terrorism and extremism, resolution of Middle East conflicts, and efforts to improve economic stability.
Medvedev and Obama instructed their governments on Wednesday to take efforts to ensure Russia's swift accession to the World Trade Organization (WTO) and create favorable conditions to boost bilateral economic ties.
Russia, the only major world economy still outside the WTO, has been in talks to join the global trade body for 15 years. The agreement of all 153 WTO members is necessary for a state to join the organization.
The accession deadline has been put off for several years already. Late last year, Moscow said it could drop its WTO ambition. Russia is still to come to terms on state subsidies to agriculture, export duties on timber and legislation to regulate certain state companies' activities.
On the controversial issue of last August's Russia-Georgia war, the leaders stressed "significant differences" remain between them, but pledged cooperation to bring stability to the Caucasus region.
Obama said they would continue talks to improve relations when he visits Moscow in July, in line with Medvedev's invitation.
