The genesis of Baby Blues comes from the award-winning, internationally syndicated comic strip of the same name. The series expands the world seen in the strip and offers stories for the whole family, exposing the humorous underbelly of suburban parenting. Set in a slice of suburbia on the outskirts of normal, this irreverent new series follows the daily exploits of Darryl (voiced by Mike O'Malley, 28 Days, Deep Impact) and Wanda (voiced by Julia Sweeney, Saturday Night Live, God Said Ha!) MacPherson. A career couple in their late 20s recently transformed into two well-intentioned but weary young parents, Darryl and Wanda are dealing with the dual pressures of their new little bundle of joy, Zoe, and the dysfunctional family living next door.

Baby Blues amplifies the comic strip's world by adding their mismatched fence neighbors, Carl (voiced by Joel Murray, Dharma & Greg) and Melinda (voiced by Arabella Field, Godzilla) Bitterman, who serve as a shining example of how not to raise children, judging by their son Rodney (voiced by Kath Soucie, Rugrats), an 8-year-old hellion who controls both sides of the fence. He is closely followed by 5-year-old Megan (voiced by Soucie) and 4-year-old Shelby. While Darryl and Wanda often wonder what past-life crimes they must have committed to deserve Rodney's constant visits to their house, baby Zoe adores this pint-sized rogue with a bowl haircut and an appetite for destruction. Adding to the mayhem is Zoe's terminally hip baby-sitter, Bizzy (voiced by Nicole Sullivan, Mad TV), an indifferent student with a penchant for bad boys. At work, Darryl's best friend Kenny (voiced by Diedrich Bader, The Drew Carey Show) is quick to accuse Darryl of bungling a domestic situation, even though his own family ranks as a priority somewhere below his golf game.