Manny and Lo are not necessarily wiser than their years: their dreams remain strangely naive. Manny expresses her fascination with "normal" family life by collecting an assortment of photos of strangers and their loved ones. Lo hopes to be an airline stewardess one day, and perfects her balance by simulating "turbulence" on Manny's weary back.

However, even the most resourceful children hit stumbling blocks. So when Lo finds herself pregnant, she convinces her sister to aid her in taking a hostage. The hostage in question, Elaine (Mary Kay Place), is a maternity shop clerk who presents herself as the world's ultimate authority on motherhood. But Elaine is very different from what she appears to be...

The delicately off-kilter humor of MANNY & LO emanates from its careful, non judgmental presentation of its characters: Lo (Aleksa Palladino), the outwardly-tough big sister who believes she's always right when she's almost always wrong; Manny (Scarlett Johansson), the more logical sister, who ignores her firm grasp of reality in order to stand by Lo; and Elaine, the self-appointed guardian of high-minded moral values who may be as much of a misfit as the girls who hold her captive. They add up to a makeshift family unit that is as topsy-turvy as it is oddly moving.