Isringhausen was, with Bill Pulsipher and Paul Wilson, a member of "Generation K", a group of highly regarded Mets prospects.

Isringhausen played catcher at Southwestern High School before being moved to the outfield at Lewis and Clark Community College.

[1] Isringhausen was chosen as a draft-and-follow prospect by the New York Mets in the 44th round of the 1991 Major League Baseball draft.

In the mid-1990s, Isringhausen and fellow minor-league pitchers Bill Pulsipher and Paul Wilson—collectively dubbed "Generation K"—were widely hyped as the next New York Mets superstars.

Still, Mets manager Bobby Valentine was reluctant to use Isringhausen in relief, saying that it would be akin to "[using] an Indy car as a taxi.

He registered a league-leading 47 saves in 2004, tying Lee Smith's franchise record (broken in 2015 by Trevor Rosenthal).

Isringhausen responded by notching career numbers in 2007, posting a 4–0 record, 2.48 ERA, and 32 saves while walking 28, striking out 54, and giving up only four home runs in 631⁄3 innings pitched, appearing in 63 games.

[5] On February 20, 2009, Isringhausen signed a minor league deal with the Tampa Bay Rays with an invitation to spring training.

[7][8] Once activated, Isringhausen pitched in nine games before it was announced on June 13 that he tore a ligament in the surgically repaired right elbow and would miss the rest of the season to undergo Tommy John surgery.

On August 15, 2011, Isringhausen became the 23rd pitcher to notch 300 career saves, which he did against the San Diego Padres in a 5–4 Mets win.

While a member of the staff at SIUE, Isringhausen denied through his agent that he was retiring from Major League Baseball, and was still looking for pitching jobs.