Here are the highlights of his remarks:
AFRICA: Obama says he's seeing the emergence of a new, more prosperous Africa even as the continent continues to face great challenges.
He called on African nations to be forceful in tackling the health, security and government corruption tests that could stunt economic progress on the continent.
The conference was aimed at shifting U.S. relations with Africa away from humanitarian aid and toward more equal economic partnerships.
Obama announced $33 billion in commitments mostly from the private sector to invest in Africa and help create jobs in the U.S.
"Africa must know that they will always have a strong and reliable partner in the United States of America," Obama said.
More than 50 African heads of state and government were in Washington for three days of talks.
EBOLA: Obama says the Ebola virus is controllable with standard public health measures and the U.S. is working with allies to send additional medical workers to West Africa.
The use of an experimental drug to treat American aid workers raises ethical questions about who should get any additional, limited supplies of a drug that's never been tested in people. Obama says all the information isn't in about whether the drug is helping.
In his words, "We've got to let the science guide us."
Obama says this outbreak has spread more rapidly than previous ones in part because affected countries' public health systems have been overwhelmed, but bolstering efforts to rapidly identify and isolate patients can work.
EXECUTIVE ORDERS: Obama says he's reviewing what authority he has to act without Congress to stop American companies from reincorporating overseas to avoid paying U.S. taxes.
Obama says the practice is unfair and not right. He says the tax income that's lost as a result must be made up somewhere and that it's usually through higher taxes or reduced government services.
Obama says he would prefer that Congress act to close the loophole, but that he's considering acting on his own to end the practice.
Republicans have criticized Obama for acting on his own in many areas, even authorizing a lawsuit against the president on the matter. But Obama says the public expects him to use his executive authority to help make their lives better wherever he can and when Congress won't send him legislation.
MIDDLE EAST: Obama says long-term stability in Israel and the Gaza Strip will come slowly and require leaders in the region to take political risks for the sake of peace and prosperity.
The president told reporters that the short-term U.S. goal for Gaza is for a temporary cease-fire to continue without being violated before it expires on Friday.
He maintained that Israel has the right to defend itself from rocket attacks and terrorist tunnels into its territory by the militant group Hamas that controls Gaza.
Obama also expressed sympathy for Palestinian Authority President Mahmoud Abbas, whose efforts to negotiate peace with Israel has so far failed.
Obama said Palestinians in the West Bank may have lost hope on how to move forward and improve their lives.
RUSSIA: Obama says U.S. sanctions against Russia over its actions in Ukraine are straining the Russian economy, which has "ground to a halt."
He also said Wednesday that if Russia invades eastern Ukraine, it would pose a whole different set of questions for the U.S.
Western officials on Wednesday warned that a Russian military buildup on Ukraine's border could herald a major incursion to protect the pro-Moscow separatists fighting Ukrainian forces.
Obama was asked about the impact of U.S. sanctions on the same day of reports that Russia plans to move to ban agricultural imports from the U.S.