She then starred in commercially successful romantic comedy films such as Knocked Up (2007), 27 Dresses (2008), The Ugly Truth (2009), Killers (2010), Life As We Know It (2010) and New Year's Eve (2011).

[8] In 1986, her older brother Jason died of injuries suffered in a car accident, after being thrown from the back of a pickup truck while out for lunch with some of his high school classmates.

She played Christina Sebastian in Steven Soderbergh's Depression-era drama King of the Hill before being cast in her first leading role in the 1994 comedy My Father the Hero.

Heigl portrayed a 16-year-old named Sarah traveling by train through the mountains with her uncle Casey Ryback (Seagal), an ex-SEAL counter-terrorist expert, in order to visit the grave of her deceased father.

Heigl had auditioned for all three of the show's female leads (the other two roles eventually went to Shiri Appleby and Majandra Delfino) before she was finally cast as Isabel, an alien-human hybrid.

[19] Heigl accepted a role in Ground Zero, a television thriller scheduled to be telecast that fall which was based on the bestselling James Mills novel The Seventh Power, in the spring of 2001.

She co-starred as a brilliant and politically-concerned college student who helps to build a nuclear device to illustrate the need for a change in national priorities.

The same year, Heigl landed the starring role in the independent film Side Effects (2005), a romantic comedy about marketing and the pharmaceutical industry, for which she was also executive producer.

A year later, Heigl was nominated for the Golden Globe Award for Best Supporting Actress – Series, Miniseries, or Television Film for her work on Grey's Anatomy.

Upon its June 2007 theatrical release, the film received generally positive reviews from critics and proved to be a box office success and a summer romcom hit.

[22] On September 16, 2007, Heigl won the Primetime Emmy Award for Outstanding Supporting Actress in a Drama Series for her role as Izzie Stevens on Grey's Anatomy.

[32] Heigl had disagreements with the character's direction in the fourth season, deeming the storyline involving Izzie's affair with George a "ratings ploy" that served to be "shocking"[26] and others speculated she would leave due to the time devotion in producing a film version of Carolyn Jessop's book Escape.

She next starred in and produced the big-screen drama Life As We Know It, directed by Greg Berlanti, which revolved around a woman and a man whose respective best friends die in a car accident.

Based on a series of novels[52] by Janet Evanovich, the film's lead character is Stephanie Plum, a bounty hunter working for a bonding company.

"[57] In 2013, she appeared alongside Robert De Niro, Susan Sarandon and Diane Keaton in The Big Wedding, a comedy about an estranged family reuniting for a ceremony.

"[61] During this period of time, Heigl broke away from her conventional romcom roles, pursuing romantic dramas, doing voiceover work, dark comedies and returning to dramatic television.

Heigl starred in the romantic drama Jackie & Ryan (2014), opposite Ben Barnes, portraying a recent single mom battling to hold onto her daughter and the love interest of a modern-day train hopper.

[64] She next starred as a rejected and jealous housewife in the dark comedy Home Sweet Hell (2015), alongside Patrick Wilson and Jordana Brewster.

[65] Variety wrote in its verdict: "Considering how often [Heigl] has been slammed for not being just another docile, eager-to-please female celebrity, it's hard not to suspect that she might have relished the chance to play an unapologetically ball-busting shrew—a grotesquely exaggerated version of a stereotype she's been assigned many times over.

Indeed, Heigl's performance as a coolly murderous model housewife is the only real reason to even consider watching Home Sweet Hell, an otherwise flailing and risible tale of adultery, extortion and suburban malaise that suggests a poor woman's Gone Girl".

In 2015, Heigl starred as the titular role in the independent film Jenny's Wedding, about a woman who finally decides to get married, but her choice of partner tears her conventional family apart.

An Indiegogo campaign was later launched to help raise money for post-production costs, and like Heigl's previous few projects, the film was distributed for a VOD and limited release in certain parts of the United States only.

[67] She starred opposite Rosario Dawson and Geoff Stults in the erotic thriller Unforgettable (2017), portraying a divorcée who torments the new fiancée of her ex-husband.

[68] Nevertheless, The Globe and Mail remarked that "Heigl works overtime to humanize the resentful mom—her face is like an old-fashioned cash register with the prices popping up—but she's more fun to watch as the story grows ugly and violent, and she unleashes the demon within".

[73] Heigl returned to form when she was cast in the USA Network legal drama series Suits, playing the role of Samantha Wheeler, a new partner at the fictional law firm of Zane Specter Litt.

Heigl was later cast in the leading role opposite Sarah Chalke and Ben Lawson for the Netflix show Firefly Lane, released in 2021.

[76] In January 2021, Heigl declared in an interview with The Washington Post promoting Firefly Lane that she was "done apologizing" for her past reputation and criticized being labelled as "difficult" in the late 2000s and early 2010s.

Her 27 Dresses co-star James Marsden defended the actress' "courage" and "strong convictions" and remarked unsurprise at her career expanding role in executive production.

[77] In September 2021, she endorsed the IATSE strike and remarked heavy criticism for speaking up about the harsh working conditions on the set of Grey's Anatomy that the crew endured, while also commenting on health and safety failures in long-hour productions.

[96] In 2012, on behalf of PETA, she signed a letter to members of the Utah legislature, urging them to reject a law that would make undercover filming in factory farms a criminal offense.