Chloe (voice of DREW BARRYMORE), a diamond-clad, bootie wearing Beverly Hills Chihuahua enjoys her luxurious lifestyle so much, she hardly notices Papi (voice of GEORGE LOPEZ), a tough looking Chihuahua who happens to be head-over-paws for the pampered pooch. But when Chloe gets lost in the rough streets of Mexico with only a street-wise German Shepherd (voice of ANDY GARCIA) to help her find her way home, Papi heads south of the border -- joining forces with a motley crew: two humans (PIPER PERABO, MANOLO CARDONA), a sly rat (voice of CHEECH MARIN) and a nervous iguana (voice of PAUL RODRIGUEZ) – to rescue his true love.