Lissette Espaillat was born on January 28th to Dominican parents in Upper Manhattan's, Washington Heights. As a child, she studied Ballet, Jazz and Modern dance. She loved dancing but after High School, she attended Parsons: The New School in NY, to get her BFA in Drama and Photography. During college, she also interned at the prestigious, Ensemble Studio Theater where her true love of acting, began. A few years later, she studied with Actor, Director and Playwright Bruce Ornstein. During this time, she went on to do various off, off Broadway plays such as "Fool for Love", "Running" and "The Captives". In 2003, Lissette was taking voice lessons with Philip Campenella in NY, when she was offered the role of 'Dulcinea' in a contemporary musical adaptation of the classic, "Don Quixote". In 2004, she started working with Bill Hopkins at the Stella Adler Acting Academy. Bill gave her the encouragement she needed to pursue more film work and in late 2004, she landed her first lead in a feature film titled "Knockout of the Century". In it she played a wife and mother, living with Aids. Other lead roles followed on both stage and screen. She played Gladys in Teatro La Tea's production of "Chained Dog", written by Rob Santana and directed by Writer, Director; Jerry Rodriguez.

"Tales of an Addict", a one woman show written by Torri Oats. In early 2005, she worked on the award winning, NYU short, "Uta" directed by Kim Spurlock, which won the 'Gestures of Reconciliation' award at the 2005 Munich Film Festival. "The Wannabe" written and directed by Althea Waslow, winner of the best documentary for "Riker's High" at the 2004 Tribeca Film Festival and another feature film titled, "Life Decisions", had been featured in the 2005,"Latino Film Festival". Also in 2005, she starred in the Feature "I Believe in America" based on the life of Albizu Campos written and Directed by Michael Narvaez. In 2008 she landed her first major film role opposite Edward Norton in the feature film, "Pride & Glory"; Directed by Gavin O'Connor. 
Around this time, she started working with Sally Dunn at T. Schreiber Studios. Since then, she has appeared on several TV shows; "Law & Order SVU", "NYC 22", and "America's Most Wanted". In 2010, she produced and starred in "By Proxy, a Night of One Acts", at the Arclight Theatre in NY. In 2012 she went back to T. Schreiber Studios to play the lead in the lab production of "The Beautiful Dark" written by Erik Gernand. In it she played a mother coming to terms with her son's mental illness. That same year, she tackled her first comedic role in the classic Neil Simon play, "Chapter II" where she played "Faye" at the Amateur Comedy Club, one of the oldest theaters in New York. 
In 2014 she played the maid of a Wall St. Millionaire (David Morse) on a TV series that as yet, has not been released. That same year she played opposite Kevin Bacon on "The Following". Most recently she played her largest TV role to date co-starring with Elias Koteas and Jason Beghe on the NBC hit series, "Chicago P.D." In it she played Mariela Hernandez an illegal immigrant who might have left a newborn baby floating in the river.