In 1991, in a 7–0 win over Salinas High School, Serafini pitched a CIF Central Coast Section playoff no-hitter.

Serafini also made one relief appearance for the Salt Lake Buzz, the Twins' Triple-A affiliate, in 1995.

It was Serafini's only major league appearance of the year, as he pitched for the Salt Lake Buzz during the remainder of the 1996 season.

In the 1999 offseason, on December 22, Serafini was traded to the San Diego Padres for minor league outfielder Brandon Pernell.

Serafini was traded to the Pittsburgh Pirates for minor-league pitcher Andy Bausher on June 28, 2000, and was assigned to Triple-A Nashville.

Serafini played for the Triple-A Indianapolis Indians for the rest of the 2001 season, and was granted free agency on October 15.

Serafini signed with the Anaheim Angels on November 3, 2001, but was released on March 28, 2002, before the season began.

In August, he briefly pitched for the Chinatrust Whales, a team in the Chinese Professional Baseball League in Taiwan.

Serafini began the 2003 season for the Triple-A Memphis Redbirds but was released on April 21, 2003, after going 0–1 with a 9.00 ERA in three games (two starts).

The next day, Serafini appeared in his first major league game since 2003, when he came in to pitch against the San Francisco Giants.

His last game was on August 26, 2012, vs the Sugar Land Skeeters—the day after Roger Clemens' notorious start with the same team.

Serafini then went back to the Mexican League, signing with the Naranjeros de Hermosillo on November 23, 2012.

[3] Circa 2011, Serafini owned the Throw Like a Pro Baseball Academy in Sparks, Nevada.

[5] On June 5, 2021, Serafini's in-laws, Robert Gary Spohr and Wendy Louise Wood, were shot by an intruder.

Also charged in the murder plot was Samantha Scott; she is described both as a close friend of both Serafini and his wife, Erin Spohr, and also as their former nanny.

Serafini made upwards of $14 million in his baseball career, but after a contentious divorce, bad investments, and a failed business, he was apparently $300,000 in debt.