Born in Reno, Nevada, Santini graduated from Bishop Manogue High School in 1955 and attended the University of Nevada, Reno where he was a member of Alpha Tau Omega fraternity.
He earned his Juris Doctor from University of California, Hastings College of the Law in 1962 and was admitted to the Nevada state bar in the same year, as well as California in 1963 and Arizona in 1966. He was in the United States Army from 1963 to 1966. Santini served consecutively as Clark County, Nevada deputy district attorney (1966-1968), Clark County public defender (1968-1970), Las Vegas justice of the peace (1970-1972) and as a district court judge of Clark County (1972-1974).
Santini was elected to the United States. House in 1974, easily unseating incumbent Republican David Towell.
He served there from 1975 to 1983, as a Democrat representing the state"s at-large district. Santini ran for United States Senate in 1982, but was narrowly defeated in the Democratic primary by incumbent Howard Cannon.
Cannon then lost the general election to former state Senator Chic Hecht. Santini was the last person to represent the entire state in the United States House, as reapportionment gave Nevada two Congressional seats as of the 1982 Congressional election.
He was succeeded by Democrat Harry Reid and Republican Barbara Vucanovich in the newly created 1st and 2nd Congressional Districts respectively.
In 1986, he switched to the Republican Party and ran for the Senate seat then being vacated by the retiring Paul Laxalt. Santini received 47% of the vote. Santini later worked in Washington, District of Columbia as a lobbyist representing a number of tourism-related interests.
Among his major clients were the National Tour Association, which retained him as a legislative counsel for government issues related to the national and international tourism industry.
Santini had been the federal legislation and regulation Washington, District of Columbia representative for National Tax Association, USA since 1983. In 1990, Santini and his family appeared as contestants on the nighttime version of Family Feud.
One of his aides appeared in a 1980 episode of the series and mentioned his name several times. Show host Richard Dawson made light of the Abscam sting operation during the opening segment of the episode.
His aide confirmed that Santini was not involved and was a "good guy".
His aide"s family lost the game to the returning champions. Santini died on September 22, 2015, in Rockville, Maryland from esophageal cancer. He was 78.
Democratic Party, Republican Party.
Member of Nevada Judges Association (president 1971).
Married Ann Marie Crane. Children: David, Lisa, Kerrie, Lorie, Mark, James Danford.