Nielsen grew up in the Washington, D.C. and Bethesda, Maryland areas, the daughter of Homer Nielsen (1912-2005), who was born in the Philippines, and Eloise (née Gerard) Nielsen (1918-2009). Her mother, a Democrat, worked in government, at one point for president Jimmy Carter, and her father was a U.S Navy captain. The family spent summers at Cape Cod. Her sister was Karen (Nielsen) Grammaticas (1951-2007), wife of Dr. Andrew Grammaticas. Her paternal grandfather was Harold Nielsen (1879-1958), who fought in World War I and had Danish ancestry. Her great-grandfather, Lewis Gerard (1833-1914), was an immigrant from France who fought for the Union in the Civil War.
She trained at Northwestern University (B.A) and the Yale School of Drama (M.F.A). At Yale her classmates included Frances McDormand and Tony Shalhoub. She is married to actor Brent Langdon.
Nielsen has appeared in several Broadway shows. Her first appearance was in the 1985 production of The Iceman Cometh as Pearl. She next appeared in Jackie: An American Life (1997) playing various characters, including Rose Kennedy and Marilyn Monroe. In 2000 she played the role of Ninetta in a new production of The Green Bird. In 2005, she played Eunice Hubbell opposite Natasha Richardson's Blanche Dubois and Amy Ryan's Stella in A Streetcar Named Desire. In 2008 she played Madame de Volanges opposite Laura Linney as Marquise de Merteuil in Dangerous Liaisons and also played Anna in To Be or Not to Be. In 2010 she played The Storyteller in Bloody Bloody Andrew Jackson.

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