Liberal cabinet minister John Milloy and Progressive Conservative John O'Toole are both calling it quits.
Milloy, currently minister of government services and government house leader, says he will continue to represent the riding of Kitchener Centre.
O'Toole has represented the riding of Durham since 1995, when the Conservatives swept to power under former premier Mike Harris.
"This has not been an easy decision," he said in a statement, adding that politics has been a way of life for over 25 years.
"Nevertheless, I feel this is the right time to open a new chapter in my life."
O'Toole had been critical of the party's so-called "right to work" policy, which would make union membership and payment of dues optional, and which caused public rifts with Tory candidates and internal dissent within Hudak's caucus.
He was applauded at a party convention last September after he warned that the party could be "screwed" in an election if it campaigned on the policy.
Last week, Tory Leader Tim Hudak did a serious about-face and announced he wouldn't campaign on it.
Milloy, who was first elected in 2003 when the governing Liberals took office, said he'd been mulling his political future for more than a year.
He had to undergo surgery two years ago to remove blockages from his heart after suffering chest pains.
"After over ten years in office, however, I feel that it is time to pursue new opportunities outside of elected life," Milloy said in a statement.
He said he wants to spend more time with his wife and two sons, aged three and eight.
Milloy served in many different portfolios. He was minister of community and social services, minister of training, colleges and universities and minister of research and innovation.
Attorney General John Gerretsen, former cabinet ministers Rick Bartolucci and Harinder Takhar and MPP Phil McNeely have also said they won't seek re-election.
Conservative Frank Klees has announced his intention to retire as well.
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