Rancic was born in Naples, Italy and moved to the United States at the age of 9. She was raised in the Washington D.C. metropolitan area. She is a graduate of Walt Whitman High School (Bethesda MD), received a bachelor's degree in Journalism from the University of Maryland, College Park, and a master's degree in Journalism from American University. While in attendance, Rancic served as a features correspondent for the syndicated university television station, covering a number of stories related to the Pentagon, Supreme Court, White House and State Department.

Her father, Eduardo DePandi, is a master tailor. The DePandi family owns Bruno Cipriani, a high-end men's clothing store in the White Flint Mall in North Bethesda, Maryland. She has a sister Monica and an opera singer brother Pasquale DePandi..

In June 2006, she released a book entitled Think Like a Guy: How to Get a Guy by Thinking Like One, a dating advice book for women in the first stages of a relationship.

Giuliana Rancic was in a relationship with actor Jerry O'Connell for about three years.

On December 16, 2006, Bill Rancic and Giuliana announced their engagement. The two married on September 1, 2007 in a ceremony on Capri at Santa Sophia Church in Anacapri. E! News - You're Squired: E!'s Giuliana Weds Apprentice's Bill - Donald J Trump | Ryan Seacrest

Giuliana Rancic appeared on The View with husband Bill Rancic to discuss her fertility issues. At age 36, she is unable to conceive. Her doctors have recommended that she gain weight in order to increase the chances of pregnancy, but as a television personality, it is extremely hard for her to accept this as an option. The next step is IVF. Bill and Guiliana Rancic suffered a miscarriage in 2010.

• She was ranked #94 on the Maxim Hot 100 Women of 2004.

Featured in People Magazine's 100 Most Beautiful of 2006 issue.