After crashing her car, getting fired, and discovering her husband is sleeping with her neighbor, a woman named Tammy (Melissa McCarthy) decides to pack up and hit the road -- with her grandmother. Visiting Niagara Falls with her granny, Pearl (Susan Sarandon), isn't exactly Tammy's first choice, but she needs to clear her head with the freedom of the open highway, and some quality time with her unconventional grandma might be just what the doctor ordered.