The episode's title refers to the subject of both the episode and the season as a whole; the state-wide (which quickly becomes nation-wide) manhunt for the Fox River 8. The series regular cast members who did not appear are Paul Adelstein (who plays Paul Kellerman) and Marshall Allman (who plays L. J. Burrows). Despite their roles as two of the eight prison escapees, the two recurring cast members Lane Garrison (who plays David "Tweener" Apolskis) and Silas Weir Mitchell (who plays Charles "Haywire" Patoshik) did not appear in this episode, though they did appear in brief flashbacks at the beginning of the episode.
The second season opens the morning after the escape, as Michael, Lincoln, Abruzzi, C-Note and Sucre barely manage — with the help of a freight train — to elude Captain Bellick. When FBI Special Agent Alexander Mahone is assigned to lead a nationwide search for the escapees, this makes their escape even more difficult. Mahone calls a press conference, and urges everybody watching the television broadcast to find the "Fox River 8."
In the meantime, Michael, Lincoln, Abruzzi, C-Note, and Sucre are found by a hunter, and held at bay when the hunter brandishes his rifle. Abruzzi holds the hunter's young daughter hostage at gunpoint, and is able to get the hunter to drop his weapon, and give Michael the keys to his Jeep Grand Cherokee. The five escapees board the SUV, presumably en route to a storage room where Michael has some items ready.
Agent Mahone and Captain Bellick use Michael's credit card invoices to find a storage room in Oswego, and each separately rush to the storage facility. It turns out to be a ruse of Michael's, as he is seen in a cemetery storage room, gathering shovels to unearth the ground at the grave of (R.I.P.) E. Chance Woods. Agent Mahone deciphers the message on Michael's tattoo ("Ripe Chance Woods") and arrives at the scene right after the escaped gang of five unearthed Michael's package and put on a fresh set of clothing. Lincoln took the backpack Michael hid and found the brothers' fake passports. The five were able to escape to Oswego and blend in, despite being tailed by Agent Mahone.
Elsewhere on the run, T-Bag raids a nearby campground, threatening campers in order to steal a hat and cooler. T-Bag finds the veterinary clinic of Dr. Marvin Gudat, and coerces him to reattach his left hand without the use of anesthesia.
Meanwhile, Dr. Sara Tancredi recovers from her drug overdose. She is interrogated by an FBI agent, who tells her that 7 more prisoners had escaped with Michael. After Nurse Katie's visit, Sara finds an origami swan inside her purse. Inside is a message "There's a plan to make all of this right", and a dotted code. The dot code on the origami swan that Sara found can be grouped into lines of numbers. The numbers are 3221243324 for the first line, 4221312231 for the second, and 23133121 for the third.
Veronica discovers yet another secret from Terrence Steadman, whose previous portrayer John Billingsley has been replaced by Jeff Perry. Steadman is being held captive, although somewhat willingly, inside the estate; the doors are locked from the outside, and the windows are bulletproof. Veronica receives a phone call from Lincoln after calling 911, and informs him of what she has learned. While she is on the phone with Lincoln, members of what appears to be The Company arrive and immediately kill Veronica for finding Terrence Steadman. Hearing the distinctive noise of gunshots after Veronica uttered her final words, Lincoln slips into grief, as his brother Michael consoles him.
Mahone continues to study images of Michael's tattoos and other elements of his escape plan, saying it will tell him everything about where Michael and the others are going, so he can be there waiting for them when they get there.
Starting with this episode, the blue-tinted graphic used in the first season's commercial bumper which were shots of prison crawlways, is replaced by a sepia-tinted graphic of racing through fields and streets, reflecting the fact that the convicts have become fugitives.
Australia's Ninemsn reports seemingly less than stellar ratings for the Australian premiere of the second season of Prison Break, "The second season opening of Prison Break attracted 1.2 million viewers, but that was hardly impressive for one of the network's most significant imports."
In France this episode was shown on November 6, 2006, not long after the finale of season one. It attracted 7.5 million viewers, and M6, the network that broadcasts Prison Break in France, received its fourth highest audience ever - 30.7% of the market share.