In 1999, Holly moved to Los Angeles to attend Loyola Marymount University.
To afford college tuition, she competed to become a Hawaiian Tropic model and worked at Hooters. Holly's appearance at these venues led to invitations to The Playboy Mansion. After more than a year of such visits, Holly was invited to move in. She became one of Hef's seven official girlfriends in August 2001. In February 2002, after all but two of his girlfriends left, Holly became Hef's "#1 Girl" and moved into his bedroom. She was named among the top Hooters girls of all time in 2008 as part of the restaurant's twenty-fifth anniversary.
Madison has spoken openly about her cosmetic surgeries, having had both a nose job and boob job. After the latter procedure, her bust measurements went from an A-cup to a D. She also once had a red Playboy Bunny logo tattooed on her lower back but later had it removed.
In 2003, Holly was the subject of a Playboy Cyber Girl of the Week pictorial on the magazine's website. She also appeared on the cover and inside of the November 2005 issue of Playboy, along with Bridget & Kendra, as part of a special pictorial promoting The Girls Next Door. The girls were featured again on the covers of the September 2006, March 2008, and February 2009 issues.
In the Season 3 episode "My Bare Lady", Holly stated that she wanted to have a career producing Playboy spreads. During seasons three and four, Holly was shown working at the Playboy studios as an intern and later a junior photo editor. She also helped design and put together The Girls Next Door 2008 calendar.
A self-described animal lover, Holly started writing articles about pets in 2006 for a friend's quarterly magazine, The Coolest Little Pet Magazine. She describes herself as "mistress of the Mansion pooches". In April 2007, Madison was featured nude in a PETA advertisement, with the tagline "I'd Rather Go Naked Than Wear Fur".
In February 2009 she quit working for the company all together due to the split from Hefner making her position "awkward".
In 2009, Madison attempted a Guinness World Record rallying women from all over Las Vegas to hold the World's "largest bikini parade ever", winning the title.
Madison was chosen to replace Jewel Kilcher on Dancing with the Stars after Kilcher was forced to withdraw (along with Nancy O'Dell) due to injuries sustained during rehearsal. She partnered with Dmitry Chaplin. On March 31, 2009 Holly and Dmitry were voted off the show in a double elimination episode.
Madison stars in topless burlesque show Peepshow at Planet Hollywood in Las Vegas. She was brought in to replace Kelly Monaco after Monaco's three month contract was up. Holly was likewise initially signed to a three month contract, but she has since extended her contract to a full year.
Like former The Girls Next Door co-star, Kendra Wilkinson, Holly stars in her own reality show, Holly's World, which revolves around her life at Planet Hollywood in Las Vegas. "It's all good-natured and not mean like other reality shows," Holly said of her show. "I'm really excited about the new series because I am also getting a legitimate co-producer credit for all the work I do behind the camera. It's not a vanity credit. I'm super excited to learn from the best and take on new responsibilities." The show premiered with a "preview episode" on December 6, 2009, and it started airing regularly in June 2010.
