What is the difference between ghetto and barrio?

Barrio is a Spanish Word meaning "district" or "neighborhood." It's not especially perjorative, and could be used in a Spanish-speaking country to describe an affluent region as well as a poor one.

Ghetto, however, originally was used for a region where Jews were forced by law to live and has come to mean, figuratively, any (generally poor and run-down) area where people of certain socioeconomic classes are forced either legally or economically to live.

In US usage, "Barrio" generally implies that a region is both a ghetto and has a large Spanish-speaking population (it wouldn't normally be used for a poor but predominantly Italian or Polish neighborhood).