For the past eighty years, believers living in the Appalachian hills of the southeastern US have incorporated handling serpents and drinking strychnine (a “salvation cocktail”) into their religious beliefs and practice. While serpent handling has been outlawed in all but two southern states, there remain several thousand practicing snake handlers today, most of whom live in poor coal mining communities. In accordance with their faith, handlers refuse medical treatment when bitten. Nevertheless, there have been fewer than 100 confirmed deaths in the history of snake handling. In They Shall Take Up Serpents, we hear the voices of believers and nonbelievers alike, widows who have lost their husbands to snakebites and wives who fear the same fate. The documentary is an intimate portrait of unwavering faith and religious ecstasy virtually unknown in mainstream American traditions.