Reign has been on Earth for a while, possibly longer than Kara. (rumor).

Reign has a daughter named Ruby March. Reign tries to hide her powers from her daughter and everyone else but is forced to use them to save her daughter when an accident happens and a statue falls on top of Ruby.

Calista Flockhart will attempt to make more appearances in the show while still remaining a guest star.

Lena Luthor and Reign are going to have an "unexpected connection" According to Jessica Queller

Character Descriptions Via Casting Calls:

ROBERT DUBOIS/BLOODSPORT – Male, 30-40s…Looking for memorable, and distinctive performers. This evil and threatening Merc is an ex-military man who has infiltrated his former base and stolen a variety of articles that he uses to cloak an underwater nuclear device. As we later learn, he is in the employ of Morgan Edge, and he has been hired to blow up the waterfront with an underwater nuke…PRINCIPAL

SAMANTHA ARIAS/REIGN – Female, late 20s to early 30s. Diverse. Samantha is a professional, young single mom (Trying to balance work and life), who begins to struggle to hold onto her humanity when an alter-ego, Reign — ruthless, righteous, superhuman — begins to take over her personality. Most important in Sam’s life is her young daughter, Ruby, who Sam would sacrifice everything to protect. ONE SEASON – FRACTIONAL SERIES REGULAR.

RUBY ARIAS – Female, Caucasian or Latina, 11 to 14. Smart, sensitive, funny, but a bit of an outsider with her peers. An independent think who doesn’t like to follow the crowd. She’s fiercely loyal to her single mother, Sam (Odette Annable) and the two make a great team, looking out for each other and enjoying each other’s camaraderie. But Ruby’s not shy about speaking up for herself – even to her mother – when she feels she’s in the right. MAJOR RECURRING GUEST STAR THIS SEASON WITH A SERIES REGULAR OPTION FOR NEXT SEASON.

GAIL MARSH – Female, Late 20s, early 30s, Open Ethnicity. The deadly and seductive PSI (aka Gail Marsh), a DC Comics foe of Supergirl, possesses psychic abilities which allow her to bring out her victim’s darkest fears. While she is a physical threat, her real power comes in bringing the Girl of Steel to her knees without throwing a punch. LEAD GUEST STAR

MORGAN EDGE – Male, 40s, Open Ethnicity. As corrupt as he is intimidating, he intends to clear the area one way or another, and he has enlisted the services of a madman to blow up the area during a special ceremony in Supergirl’s honor. This savvy and formidable titan of industry is pushing through a huge new redevelopment plan for the city’s waterfront – and he doesn’t care if he has to uproot the entire indigenous immigrant population to implement his money-grubbing scheme. …RECURRING GUEST STAR

Maggie Sawyer does not die, as confirmed in an article from Entertainment Weekly. Executive Producer Andrew Kreisberg said:

Maggie does not die. I’m sure a lot of people are afraid of that. Maggie will continue to exist in the world and we hope that if the opportunity presents itself for her, that she’ll come back from time to time. Unfortunately, Floriana decided to move on, which left us with, how do we write her out as a regular while still honoring these two women who were deeply in love with each other? Taking a page out of some of our own personal dating history, we’ve come up with a story that we really feel like honors what’s come before them, and honors how much they love each other, how much they mean to each other, and how much they’ve changed each other’s lives. It’s some of the most emotional stuff we’ve ever done, and Floriana has been so good in these first five episodes. Episode 3 is all about Maggie and her dad, played by Carlos Bernard, and it’s some of the most heartbreaking stuff I’ve ever done on anything I’ve ever done.

Kara and Lena will have many more adventures as the season begins. In a spoiler room article, Entertainment Weekly spoke to Executive Producer Andrew Kreisberg who said:

Lena and Kara’s friendship will continue to grow. There’s a lot of Lena-Kara adventures early on in this season. The most interesting thing about Lena is that she is so good, and so moral, and believes in second chances, but she comes from this family of truly evil people. As people are going to realize over the course of this season, it doesn’t take much to make you bad. People don’t just turn evil. They do one small bad thing and then that leads to another, and then to another, and so any time you’re watching Lena, you’re always wondering, ‘Is this the moment when she does the one small thing?'

According to another Entertainment Weekly Spoiler Room, Katie McGrath says she is going to go some lengths to help Kara in her time of need after Mon-El's departure:

While Lena’s feeling good that she helped saved the world, she feels very responsible that her best friend is hurting, and she’s trying to bring Kara back to the friendship that they had.

Katie went on to tease that Lena will do something very big in the premiere to try to rectify that.

According to TV Guide, Reign's story will be a dividing one for team Supergirl. Expect these three things for season three:

1. She's a ticking time bomb. The season finale showed Reign being sent to Earth from Krypton as an infant. She was genetically created on that planet to be a weapon of mass destruction, executive producer Andrew Kreisberg says. "But she has no idea! She has been living in National City as [a now grown-up] person named Samantha Arias."
2. She is breaking the Arrowvers's "evil" mold. "One thing we've never done on Arrow or The Flash is watch the villain become the villain," Kreisberg says. "Sam is just Sam." But as the season progresses, the working single mom "will realize there is something different about her", Kreisberg continues. "It's a fun dark-mirror version of the journey Christopher Reeve took in the original Superman as Clark".
3. She'll divide the team. Sam will develop connections with Supergirl's core characters which will cause friction down the road. "Everyone will have a relationship with her, and that will drive much of the season in terms of how far they're willing to go to stop her when she becomes Reign", Kreisberg explains. "Some will believe she need to be saved; others will think she needs to be stopped."

At Comic Con 2017 this year Melissa told us that Supergirl's costume wouldn't change, however, according to a recent spoiler room from Entertainment Weekly, we will see her is something different for a time.

There is a different suit that I will be wearing at some point this season, but I won’t tell you when or to what capacity, It’s cool, though.