As Coulson, Mack and Fitz attempt to track down and neutralize a rogue group looking to end Inhuman Registration worldwide, Simmons and Dr. Radcliffe only have hours to save May before she succumbs forever to her mysterious illness.
Following the blackout, the Watchdogs anonymously send a threatening online message, claiming they are Inhumans, and that they will shut off more cities hour by hour if the Sokovia Accords are not shut down. Phil Coulson and Jemma Simmons are overlooking Melinda May's vitals, fearing for her life, when Chen's heart rate spikes dramatically before he passes away from Lucy Bauer's infection. Simmons realizes the same will happen to May in just hours if they do nothing. Jeffrey Mace assigns Simmons to try to save May and assigns Coulson to Miami.
Elsewhere, the same blackout happens to Los Angeles, so Robbie Reyes and Daisy Johnson quickly go to check on Gabe Reyes, who happens to be attacked by a gang when they arrive. The two vigilantes take down the gang members and bring Gabe home.
Meanwhile, Holden Radcliffe prepares to help Simmons save May, who is hallucinating almost everything around her to be graphically demonic at this point. After they calm her down, they realize the only way to save her is to kill her and then quickly bring her back to life before she completely shuts down, which would "reset" her brain. They kill her as planned, and although the power goes out before they can perform CPR, Radcliffe eventually uses Aida's battery to allow proper CPR, which luckily brings May back to life and cures her.
Meanwhile, as Coulson, Alphonso Mackenzie, and Leo Fitz enter Miami, their car suddenly shuts down, along with Coulson's Prosthetic Hand and the rest of their gear. Watchdogs invade the party that Yo-Yo Rodriguez was attending, looking for an Inhuman there. At that moment, Coulson, Mackenzie, and Fitz arrive and, with Yo-Yo, subdue the Watchdogs.
Elsewhere, Robbie Reyes and Johnson arrive at their home. Reyes then heads out to make sure people are safe as the Ghost Rider, using work as an excuse, not wanting Gabe to know what he truly does. Gabe and Johnson have a conversation after he leaves, but Gabe tells her he knows of her abilities, and he wants him to stay away from Robbie, threatening to expose her to the public if she does not.
Meanwhile, Coulson, Mackenzie, Fitz, and Rodriguez find the source of the outages, an EMP device, and reset it to bring the power back.
The next day, Director Mace announces S.H.I.E.L.D. as an official agency again, finally ending two and a half years of hiding in the shadows. Robbie returns to their home to discover Johnson left in the night, leaving Gabe alone.
- Clark Gregg as Phil Coulson
- Ming-Na Wen as Melinda May
- Chloe Bennet as Daisy Johnson/Quake
- Iain De Caestecker as Leo Fitz
- Elizabeth Henstridge as Jemma Simmons
- Henry Simmons as Alphonso Mackenzie
- John Hannah as Holden Radcliffe
- Gabriel Luna as Robbie Reyes/Ghost Rider
- Parminder Nagra as Senator Ellen Nadeer
- Natalia Cordova-Buckley as Yo-Yo Rodriguez
- Jason O'Mara as Director Jeffrey Mace
- Lorenzo James Henrie as Gabe Reyes
- Mallory Jansen as Aida
- Valery Ortiz as Maria
- Derek Hughes as Mertz
- Alexander Wraith as Agent Anderson
- Patrick Cavanaugh as Agent Burrows
- Preston Flagg as Darryl
- Stephanie Maura Sanchez as Leticia
- Dale Pavinski as Briggs
- Jen Kuo Sung as Chen
- Ricky Saenz as Pistol Punk
- Aaron Gaffey as Mysterious Figure
- Michael Cory Davis as Agitator
- Devon Libran as Slugger Punk
- Adriana Diaz as Hostage
- Jake Green as Terrified Driver
- Matt Emig as Watchdog (uncredited)
- Jeremy Marinas as Watchdog (uncredited)
- Christopher Troy as Punk (uncredited)
- Los Angeles, California
- Miami, Florida
- Washington, D.C.
- New York (mentioned)
- Pasadena, California (mentioned)
- Pasadena Momentum Laboratory (mentioned)
- London, England (mentioned)
- Moscow, Russia (mentioned)
- Buenos Aires, Argentina (map)
- Athens, Greece (map)
- Phil Coulson's Prosthetic Hand
- Bulletproof Vest
- Rapid Bone-Healing Pills
- Backscatter X-Ray Eye Implant
- Asset Communication Device
- Sokovia Accords (mentioned)
- WHiH World News
- Roxxon Corporation
- Momentum Labs (mentioned)
- United States Armed Forces (mentioned)
- HYDRA (mentioned)
- Strategic Scientific Reserve (logo)
- Fifth Street Locos (mentioned)
- CDC (mentioned)
- International Affairs (mentioned)
- Lincoln Campbell
- Eli Morrow (photo)
- Lucy Bauer
- Matthew Ellis
- Nick Fury
- Carrot Top
- Hot Wheels
- Senator Nadeer was credited as "Rota Nadeer" in this episode, but her full name was confirmed to be "Ellen Nadeer" in the episode Lockup.
- Uprising is the only episode in the Ghost Rider arc in which Robbie Reyes doesn't change into the Ghost Rider.