The show also offers a few throwbacks for longtime viewers with scenes that are reminiscent of the shows earliest days.
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"I think we definitely wanted to acknowledge and be respectful of the origin story," said Caterina Scorsone, who plays Dr. Amelia Shepherd. "Tipping of the hat to where we've been, and the beginning of this journey for the first intern class that we journeyed with and now we have this other beautiful intern class."
James Pickens Jr. has played Dr. Richard Webber on the drama series since it started in 2005.
Things didn't end well for Dr. Webber at the end of last season. Pickens says he's happy his character gets a fresh start.
"I think he's really excited about these young interns, and seeing where they go, and he wants to kind of steer that ship, as he's done through these 19 seasons and various iterations," said Pickens. "I think that's its redemption. It's redefinition in some ways. I think these young people are going to be the catalyst for that."
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Chandra Wilson is also an original cast member on "Grey's," playing Dr. Miranda Bailey.
As they move into year 19, Wilson observes that everything old is new again.
"The journey of the intern doesn't change, right? It's the same. So the only difference is, when we were watching it in the first season, it was all new to us. But now we have an audience member watching when you can kind of anticipate a little bit, like where are they going? That's exciting," said Wilson.
"Grey's Anatomy" airs Thursday nights on ABC.