She served on the New York City Council before winning a special election to the House of Representatives in 1990 as a Republican to replace her father, who retired from Congress to become Staten Island Borough President.

[3] On January 1, 1990, her father, incumbent Republican U.S. Representative Guy Molinari, decided to resign in order to become Borough President of Staten Island.

On the eve of the special election, The New York Times endorsed Molinari because she "promises to add a moderate Republican voice to the city's Democratic-dominated congressional delegation".

She signed on to the Republicans' 1994 Contract with America, which promised a balanced budget amendment to the U.S. Constitution, and opposed the placing of U.S. troops under UN command.

[9] She also sided with the Democrats in voting for the Family and Medical Leave Act (FMLA), a cornerstone of Bill Clinton's social policy.

She offset these positions with her own standing as a new mother, framing her outlook in terms of "family values", and in fact energetically campaigned for fellow Republicans with whom she disagreed on both abortion and FMLA.

Ward to acquire the Staten Island Railroad to re-establish freight service to the Howland Hook Marine Terminal.

[11] As Molinari put it on the House floor in 1994, the rules "strengthen the legal system's tools for bringing the perpetrators of these atrocious crimes to justice.

"[12] In her autobiography she intimated that the tense ideological atmosphere within the Republican Party after they won majority in the House and Georgian Newt Gingrich became Speaker contributed to her unease.

Molinari gave the keynote speech at the 1996 Republican National Convention, but resigned from the House in June 1997 to take a job as a television journalist for CBS.

The firm is home to former New York City Mayor Rudolph Giuliani and has a well-established government relations and strategic communications practice.

Her activities have included sponsoring legislation, and more recently heading a task force directed toward developing an Internet-based counterpart to the existing hotline.

Molinari also serves as Chair of The Century Council, a not-for-profit organization dedicated to fighting drunk driving and underage drinking by advocating and facilitating education, communications, research, law enforcement, and other programs.

In 2013 Molinari was a signatory to an amicus curiae brief submitted to the Supreme Court in support of same-sex marriage during the Hollingsworth v. Perry case.