Nestled in the Appalachian Mountains of Virginia, the tiny town of Big Stone Gap is home to some of the most charming eccentrics in the state. Ave Maria Mulligan is the town's self-proclaimed spinster, a thirty-five year old pharmacist with a "mountain girl's body and a flat behind." She lives an amiable life with good friends and lots of hobbies until the fateful day in 1978 when she suddenly discovers that she's not who she always thought she was. Before she can blink, Ave's fielding marriage proposals, fighting off greedy family members, organizing a celebration for visiting celebrities, and planning the trip of a lifetime-a trip that could change her view of the world and her own place in it forever.

Recently relocated from San Francisco to conservative suburbia by her lesbian mothers, Tru struggles like all teens to fit in and find love, but her quest is complicated by sexual politics, closed minds, and closeted friends as she seeks to establish her school's first Gay-Straight Alliance.

After the departure of Rube Sofer, a new head reaper named Cameron Kane takes over. He's a slick businessman who couldn't care less about helping the newly dead. Chaos ensues and brings out the worst in Daisy and Mason who begin drinking anew. George and Reggie re-connect for the first time when George reaps a new friend of Reggie's.