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America's Most Wanted: America Fights Back takes on the nation's hottest crime issues. This crime-fighting program focuses on capturing fugitives, protecting victims and empowering citizens within the criminal justice system. The series also takes an in-depth look at laws that harm victims, champions the cause of lawmakers fighting to protect victims' rights and presents news of recent captures, convictions and missing children cases.

The show's nature does not allow repeats, except for updates on convicted criminals, and is preempted a maximum of eight times during the year; however, if a fugitive featured on the show is not captured, their profile may be aired again.

The first two-hour quarterly special aired on Saturday, October 29, 2011 on FOX. The second two-hour special aired on Saturday, December 17, 2011, the third two-hour special aired on Saturday, February 11, 2012, and the fourth and final two-hour special aired on Saturday, April 21, 2012.

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After the program’s pilot aired, a lengthy search was conducted, and John Walsh was selected as the host of the show; other potential candidates included former Marine Corps Commandant General P. X. Kelly and victims' advocate Theresa Saldana. Walsh had gained publicity after his six-year-old son, Adam Walsh, was kidnapped and murdered in 1981. Walsh and others had successfully advocated Congress for the creation of the National Center for Missing and Exploited Children.

The show usually ends with John Walsh saying, "...and remember, you can make a difference", or, on occasion, "...and remember, you do make a difference."

John Walsh is one of those rare individuals who has turned a horrifying personal tragedy into an unmatched strength. I cannot thank him enough for championing the rights of the victims of crimes in a society that seems to care more for the rights of the criminals. This is a man whose mission in life is to speak on the victim's behalf and put the scumbag criminals where they should be.