Klum became known for her appearances in the Sports Illustrated Swimsuit Issue and the Victoria's Secret catalog. In addition to modeling, she has appeared in several TV shows, including Spin City and Sex and the City. She had a role as an ill-tempered hair model in the movie Blow Dry, played a giantess in the movie version of Ella Enchanted and was cast as Ursula Andress in The Life and Death of Peter Sellers.

In December of 2004, she became the host of the reality show Project Runway on the U.S. cable television channel Bravo, in which fashion designers compete for the opportunity to show their line at New York Fashion Week and receive money to launch their own fashion line. She also received an Emmy Award nomination for the show for the first and second seasons.

In December of 2005, in addition to hosting the second season of Project Runway, she became the host of Germany's Next Top Model, the German version of America's Next Top Model, which aired on the German network ProSieben. The show was a ratings success, but was not without controversy. German feminist groups encouraged boycotts of the show after one of the contestants was eliminated after being told she was "too big". Several politicians also accused the show of promoting anorexia and other eating disorders.

Klum created her own clothing lines (including one for infants) that were featured in the German mail-order catalog "Otto". She also has designed shoes for Birkenstock, jewelry for Mouawad, and swimsuits - featured in the 2002 Sports Illustrated Swimsuit Issue - that, for a limited time, were available for sale through her personal website.

She also produced her own fragrance, called "Heidi", which is currently available for sale through her own website.

She is an avid painter and has had several of her paintings appear in various art magazines in the U.S. On September 27, 2002 she dedicated a sculpture she painted called "Dog With Butterflies" to commemorate the role of rescue dogs in the aftermath of September 11. She has also had a rose named after her, known as the Heidi Klum rose.

Klum is featured in the 2004 James Bond video game Everything or Nothing, where she plays a villain Dr. Katya Nadanova.

Klum married celebrity hairstylist Ric Pipino in 1997. The couple divorced in November 2002. She has also dated Red Hot Chili Peppers frontman Anthony Kiedis.

Klum has a daughter, Leni, named after Klum's grandmother, who was born on May 4, 2004. Her father is Klum's former boyfriend, Flavio Briatore. Klum's husband, British musician Seal, is helping her raise the child. Seal refers to Leni as his child.

Klum and Seal were wed on May 10, 2005, on a beach in Mexico. Klum gave birth to their son, Henry Günther Ademola Dashtu Samuel, in Los Angeles on September 12, 2005. He is named after his father, whose birth-name is Henry, Heidi's father Günther, Seal's father Ademola and after a Navy jet, the Dash Two. As the Dash Two watches over the main jet, Henry is supposed to watch over his sister. Klum revealed the meanings of her son's several names on her TV show, Germany's Next Top Model.

In June 2006, Klum and Seal announced that they are expecting another child. Seal told People, "It gives me great joy to announce that Heidi, Leni, Henry and I are expecting a new addition to our ever increasing family. We all feel both excited and fortunate to be able to share this experience once again." On November 22, 2006, in Los Angeles, Heidi gave birth to their second son: Johan Riley Fyodor Taiwo Samuel, who was born at 5:01 pm PST weighing 8 lbs 11 ounces. Seal posted on both his and Heidi's site the following: "To our children, a brother. To our parents, a grandson. To my wife and I, a son. To our family, a blessing. He is healthy, beautiful and looks just like his mother."