It's Monk's twenty-fifth college reunion, and Monk returns to the University of California at Berkeley campus to reconnect with his old friends. Unfortunately, Monk must quickly face the fact that most of his old classmates remember him not as Adrian Monk, but as "Captain Cool," so named because of his penchant for defrosting refrigerators. However, there is one woman who remembers Monk, an old friend of Trudy's named Dianne Brooks.
While Monk tries to enjoy the reunion, Captain Stottlemeyer pays him an unexpected visit. A former university nurse has been murdered, and the captain has reason to believe that the killer is an attendee at the reunion. Monk's friend Dianne was close with the nurse, and is saddened by the news of her death. Meanwhile, Dianne's husband, Kyle, is acting strangely. He insists that everyone eat lunch at an old Berkeley hangout, he insists on calling one of their lunch companions, a woman who calls herself Gertrude, "Trudy," and later, he pushes everybody into a game of touch football that nobody wants to play.
Then, at a reunion banquet, Capt. Stottlemeyer makes a discovery. Dianne is wearing a pair of earrings that match a necklace that he found at the nurse's murder scene. With this bit of information, Monk makes a startling realization: Kyle killed the nurse, and he is about to kill Dianne!
Monk explains what is going on. Recently, Kyle found a 25 year-old suicide note written by Dianne. He realized that with that note, he could kill his wife, and leave the note behind to make her death look like a suicide. The note was in her handwriting, so nobody would question it. He only had one problem: the note was written when she was in college, so he had to orchestrate people and events at the reunion to "match" the people and events from Dianne's suicide note. That's why he's been acting so strangely. The university nurse had to die because she read Dianne's note twenty-five years ago. Monk leads everyone to the hotel room where Kyle and Dianne are staying, and they get there just in time to stop Kyle before he pushes Dianne off the balcony in the final step to his horrific plan.
After an eventful reunion, Monk leaves his alma mater with another case solved, and some bittersweet memories of his college days spent with his beloved Trudy.