Dr. Zalost is first seen speaking to the mayor of Nowhere, demanding $33,333,333,333 for his Unhappy Cannonballs project. The mayor and his adviser laugh it off, and Zalost threatens to use Nowhere as research if they don't pay, which would make the citizens "very...unhappy." The mayor counters by saying that they were already unhappy due to the recent increase in taxes, and tells Zalost that if he tries to bamboozle them again he'll be thrown in jail before kicking him out.
As threatened, Zalost unleashes the cannonballs on Nowhere, leaving everyone aside from the mayor and his adviser too depressed to move. The mayor subsequently yields to Zalost's demands, but Zalost refuses to reverse the effect, since the money failed to make him happy.
Meanwhile at the Bagge farm, Courage is helping Muriel with her "Happy Plums," which can supposedly make anyone happy. Eustace gets impatient waiting for the paper, and, after seeing a brief report on the news concerning the attacks from Zalost's tower. Eustace drives up to get the missing newspaper himself, only to discover that none have been printed.
On his way back to the farm, Eustace encounters Zalost's tower blocking the road, and honks at him for having it parked in the road, drawing Zalost's attention. Zalost subsequently follows Eustace back to the farm and unleashes his cannonballs, which have no effect on Eustace (whom Zalost deems immune to emotions). Courage manages to evade the cannonballs, but Muriel is struck and falls into depression.
After many unsuccessful attempts to help her, Courage infiltrates the tower with a bit of help from Eustace. Courage enters a large room containing mountains of cannonballs lining the room along with a giant cauldron in the middle, filled with green liquid that changes ordinary cannonballs into unhappy cannonballs.
Rat then attacks Courage, who attempts to use the cannonballs to his advantage. Rat is hit by one, and grows into a monstrous rat who leaps at Courage. Courage slings some of Muriel's Happy Plums into his mouth, changing him into a harmless baby rat wearing a diaper.
Courage ascends the staircase to the tower's keep, where Zalost hogties him and points a cannon at him. He informs Courage that if he can win a game of Hangman before the cannon goes off, he, Dr. Zalost, will cure Muriel.
After several wrong guesses – and a fiasco trying to buy vowels – Courage guesses the word, BOOM, without guessing the consonants first. Zalost accuses Courage of cheating and starts firing at the dog.
After Zalost gets a hold of Courage, Zalost prepares to drop our hero into the cauldron. Courage throws the cup of Happy Plums at Zalost, however, the plums bounce off of the depressed doctor's head and falls into the cauldron. Zalost drops Courage, who clings to the edge of the staircase, while the liquid in the cauldron turns pink and starts shooting out pink cannonballs.
Zalost moans as he descends the now crumbling tower, which begins to shoot out pink cannonballs like a volcano, restoring all of Nowhere to happiness. Courage emerges from the rubble, holding the baby Rat and one pink cannonball. Zalost follows him back to the house, holding his last unhappy cannonball. Courage uses his cannonball to heal Muriel, then runs into the kitchen. Zalost's cannonball hits Eustace, who is seemingly petrified.
Courage and Muriel hide under the table, and Zalost is momentarily distracted by the plums on the table. He eats some, coughs, then looks under the table, his skin is now normal-colored. Muriel's Happy Plums cured his depression, and the last scene shows Dr. Zalost hugging the still baby Rat.
- One of the few episodes where Eustace actually works with Courage to help save Muriel. The other was The Demon in the Mattress.
- Dr. Zalost's name is a reference to Zoloft, a powerful antidepressant drug, an SSRI. It is used to treat depression and the happy plums could be a reference to the drug.
- Dr. Zalost name translates to "Sorrow" in Croatian (also many other Slavic languages). He was inspired when John R. Dilworth was in Zagreb, Croatia. This is likely a reference to his depression.
- This is the first time that Nowhere was in trouble, a similar plot was later used in Curtain of Cruelty and King of Flan.
- This is the last episode to have the "The End" Title card since The Magic Tree of Nowhere.
- Last episode of 2001.