
Vlad is back, only now he's afflicted with a serious case of ecto-acne, a direct result of the college lab accident with Jack and Maddie. To ensure Danny helps him find a cure, Vlad infects Sam and Tucker with his disease, and Danny turns to Clockwork for help. Danny convinces Clockwork to let him go back in time to make sure the accident that injures Vlad never happens. Unfortunately, when he changes the past, he changes the present. When he arrives back in the present day, Maddie is married to Vlad and living in Wisconsin, and Jack's a ghost named Jack Plasmius! Now, Danny must go back in time for a second time to ensure his parents get together, but when he does, will that mean ecto-acne doom for Tucker and Sam?
Danny and Sam get into a fight, and when Sam utters the words, "I sometimes wish I'd never met you," she finds herself in a world in which she and Danny are strangers. Worse than that, since it was Sam who encouraged Danny to check out the Fenton Portal the night he got his ghost powers, Danny doesn't have any powers! Now, Sam must convince Danny that they share a friendship and a history, and lead him back to the Fenton Portal for a second "accident" so he can again become Danny Phantom.
After being bitten by tiny green ghost beetles, the kids of Casper High get a mysterious illness that gives them ghost powers and are quarantined at a spooky old hospital outside of town. When Danny sneaks into the hospital to investigate, he is captured by Penelope Spectra and her assistant, Bertrand. They are the ones who started this illness as part of their plan to build Penelope a young and beautiful new body. All she needs is Danny's half-human/half-ghost DNA to complete her ghostly plan. With Danny captured and Sam sick, it's up to Tucker to conquer his fear of hospitals and free Danny before Penelope gets what she's after.