As children in 1918 Baltimore, Annie, an Irish-American girl, and Vince, the son of Sicilian immigrants, both lose loved ones-Annie's father and sister to the Spanish flu and Vince's brother to an auto accident. The tragedies change how each of them face the world and-after they meet and wed-how they relate to each other. Together and sometimes apart, they overcome discrimination, illness, a family rift, a son going off to war, and marital strains caused by Vince's ambitions and marital infidelity and Annie's passivity and fear of change. With its focus on the children of immigrants in a major US city, Once Upon a Time in Baltimore presents a vivid and moving picture of family struggles and triumphs amid the ever-changing social mores, historical upheavals, and dark challenges of 20th century America.