Broadway breakthrough and other roles (1998–2005) While still at Juilliard, Ramírez was discovered by a casting director and was offered the role of Wahzinak in
Paul Simon's 1998
Broadway musical
The Capeman. Based on the life of the Puerto Rican gangster Salvador Agron, the production garnered negative reviews. They made their screen debut in the same year, with a minor role in the romantic comedy ''
You've Got Mail''. Starring
Tom Hanks and
Meg Ryan, the film had Ramírez play Rose, a
Zabar's cashier who was "
very serious about her line's cash-only policy." Ramírez's first voice acting role was the titular protagonist of Lammy, an anxious guitarist, in the 1999 video game
Um Jammer Lammy. The game was a guitar-based spin-off of
PaRappa the Rapper exclusive to Sony's
PlayStation console, involving Lammy getting to her band's concert within a tight fifteen-minute window. In 2001, they reprised their role in
PaRappa the Rapper 2, a series sequel developed for
PlayStation 2, but had a smaller role involving a cameo appearance during the song "Hair Scare". Ramírez also voiced Lammy in promotions for the CD release of in-universe girl band MilkCan's album
Make It Sweet!, and
FMV cutscenes included in the arcade version of the game entitled
Um Jammer Lammy NOW!. In 1999, Ramírez appeared in Mark Lamos's ''The Gershwins' Fascinating Rhythm
(1999). They garnered praise for their performance and received an Outer Critics Circle Award nomination for their role. Charles Isherwood of Variety'' praised their "beautiful, smoky voice" but was critical of their "torchy" performance of "The Man I Love," which ignored "the wry irony that infuses Ira's lyrics". Ramírez then appeared in the 2001 Broadway production of
Edward Kleban's
A Class Act. They replaced Julia Murney (from the
off-Broadway) to play the role of Felecia, the protagonist Ed's boss. The same year, they starred in other productions including
Fascinating Rhythm and
Dreamgirls, and then performed in the 2002 production of
The Vagina Monologues with
Tovah Feldshuh and
Suzanne Bertish. During this time, Ramírez also appeared in guest roles in several television series, including
NYPD Blue,
Law & Order: SVU,
Third Watch, and
Spin City among others. Ramírez's breakout role came upon being cast as the Lady of the Lake in
Eric Idle and
John Du Prez's musical
Spamalot. Based on the 1975 film
Monty Python and the Holy Grail, the musical opened on Broadway in 2005 to widespread acclaim. Ramírez was singled out for their performance, winning several awards including the 2005
Tony Award for Best Featured Actress in a Musical and the
Drama League Award for Distinguished Performance. Ben Brantley of
The New York Times described them as "a toothsome devourer of scenery", and another reviewer for The Playgoer emphasizing their stage presence remarked that their "intensity is totally serious and totally ludicrous and totally on key". An
Entertainment Weekly review gave them the highest praise by calling them a show-stealer.
''Grey's Anatomy'' and other projects (2006–2021) After success on Broadway, Ramírez joined the cast of the
ABC medical drama ''
Grey's Anatomy'' in a recurring role as
Dr. Callie Torres, a love interest for Dr.
George O'Malley, in the show's
second season. On a special ''Grey's Anatomy
-themed episode of The Oprah Winfrey Show, Ramírez revealed that top executives from ABC, who were greatly impressed by their performance in Spamalot
, offered them a role in any ABC show they wanted. Ramírez picked Grey's'', as they were already a fan of the show. Ramírez further explained that at their initial audition, the producers liked them and intended to add them to the show but did not know who to cast them as. Ramírez also said they were in awe of how the executives said, "Pick a show, any show," explaining that it is rare. The series creator and executive producer,
Shonda Rhimes explained, "I was looking for a girlfriend for George, but it was in the infancy stages, so I had no idea what I was looking for." Rhimes built the character around Ramírez after Rhimes met them. Ramírez, who was initially given a recurring status at the time of the character's inception, received a star billing in the show's
third season, alongside fellow cast member
Eric Dane, who portrayed
Dr. Mark Sloan. Ramírez provided
a cappella vocals in the song "
Silent Night" for the soundtrack of the show's sixth-season episode "Holidaze," airing on November 19, 2009. Ramírez served as the main vocalist for the musical episode of ''Grey's Anatomy'', "
Song Beneath the Song", which aired on March 31, 2011. Marcus James Dixon of Gold Derby called them the "show-stopper" and wrote that they "stole the show in a gut-wrenching performance worthy of an
Emmy award." As the series progressed, the character's popularity soared and Ramírez garnered widespread recognition and critical acclaim for their portrayal of a complex character on television. Maggie Fremont, a TV critic for
Vulture, reviewed Ramírez and
Jessica Capshaw's performances during an 11th season episode, calling them "goddesses walking amongst mere mortals". Ramírez was nominated for Outstanding Actress in a Drama Television Series at the
Alma Awards in 2007 and 2008. Also in 2007, at the
13th Screen Actors Guild Awards, the cast of Grey's Anatomy received the
Award for Outstanding Performance by an Ensemble in a Drama Series. They and the cast were nominated for the same award in 2008. In 2011, at the 42nd
NAACP Image Awards, Ramírez was nominated for
Outstanding Supporting Actress in a Drama Series.'''' In May 2016, Ramírez left the show at the conclusion of the 12th season, after having played the character for a decade. They released a statement saying, "I'm deeply grateful to have spent the last 10 years with my family at ''Grey's Anatomy'' and ABC, but for now I'm taking some welcome time off." Ramírez turned producer with the 2016 teen comedy film,
Loserville. The project was released in partnership with the Pacer Foundation's Center for Bullying Prevention & Stomp Out Bullying. From 2017 to 2019, Ramírez co-starred in the fourth and fifth seasons of the
CBS political drama
Madam Secretary, replacing
Bebe Neuwirth, who played Nadine Tolliver. They played Kat Sandoval, the new policy advisor of Secretary
Elizabeth McCord (
Téa Leoni). In 2021, Ramírez was cast as non-binary podcast host and comedian Che Díaz in the
Sex and the City revival series
And Just Like That.... The character of Díaz has received universally negative reviews from fans and critics, with Kevin Fallon of
The Daily Beast calling them "the worst character on TV." ==Personal life==