On June 5, 2015 ABC announced that Jason George has been promoted to series-regular status after having performed a recurring role as Dr. Ben Warren since the sixth season of the medical drama.

In the tenth episode of the season, Giacomo Gianniotti was also promoted to series-regular status as intern Andrew DeLuca.

TV critics and analysts noted the renewed interest in viewership with Rich Kissell of Variety calling it a 'renaissance.

Meanwhile at the hospital, Alex is faced with a terribly difficult decision after newborn twins, Emma and Daniel, need liver transplants; however, only one of the parents is a match, and no other donors can be found.

Owen and Amelia later bond over their imperfect lives, Alex continues to be Meredith's person, and Jo and Stephanie fail to mend their friendship.

Once Arizona breaks April’s news to Jackson, the couple argue over raising the baby together versus separately.

Penny is named the winner of the grant, which shocks Callie and upsets Stephanie, who thought Amelia was in her corner.

The doctors find themselves going through a rollercoaster of emotions after two 8-year-old boys end up in the ER due to a gunshot wound caused by playing with a gun.

Alex gets upset when Jo reveals that she keeps a gun underneath their bed, and Maggie gets scared thinking about being responsible for watching Meredith’s kids.

[32] Production began on May 21, 2015, when Rhimes announced on Twitter that the writers were in full swing mapping the twelfth season.

[37] Because of the annual Halloween television special It's the Great Pumpkin, Charlie Brown, the twelfth season had a hiatus on October 29, 2015 following the 250th episode.

"[42] During an interview with TVLine, Shonda Rhimes said that the twelfth season will take "a much lighter tone" in the wake of Derek's death.

[42] On May 2, 2014, the rest of the 6 original cast mates, Justin Chambers, Chandra Wilson and James Pickens Jr., excluding Sandra Oh, renewed their contracts for another two seasons (11 and 12) as Drs.

[49] It was announced on June 15, 2015, that Martin Henderson, who played a doctor on the ShondaLand produced show Off the Map, would be added as a series-regular for the twelfth season.

[51] It was announced on September 11, 2015 that Chasing Amy actress Joey Lauren Adams would guest star as Dr. Tracy McConnell, Dr. Bailey's opponent for Chief of Surgery, and appeared in the season premiere.

[52] TV veteran Bill Smitrovich was announced on November 12, 2015, to guest star as a therapist in the tenth episode of the season.

[54] It was announced on January 8, 2016 that Maya Stojan will appear in 1 episode as a guest-star which later turned out to be Jackson's patient Tatiana whom he treated over several years.

[56] Variety announced on March 8, 2016, that Wilmer Valderrama was cast as Kyle Diaz, a recurring role which he will play in a multi-episode arc.

[57] The season marked the last appearance for long-time cast member Sara Ramirez who played Dr. Callie Torres on the series since 2006.

[58] Her character was involved in a custody battle with ex-wife Dr. Arizona Robbins, played by Jessica Capshaw, which led to the former's move to New York from Seattle.

[59] On May 19, in a note posted on Twitter after the season finale, Ramirez wrote that she was “taking some welcome time off.”[60] Rhimes replied to the tweet by saying, “I will miss Callie tremendously, but am excited for what the future holds for Sara.

She will always have a home at Shondaland.”[60] Later, speaking at the Vulture Festival in New York City on May 22, Rhimes, told that she didn't know that Ramirez was leaving until they had shot the finale.

Club's Caroline Siede described the twelfth season of Grey's Anatomy as "phenomenal", stating that the series underwent a "powerful renaissance this year".