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Pamela Anderson was repeatedly referenced in the 2006 comedy film Borat: Cultural Learnings of America for Make Benefit Glorious Nation of Kazakhstan as the title character seeks to kidnap and marry her. Anderson appears in person at the end of the film confronted by Borat in a staged botched abduction.

Pamela Anderson performed on February 13–14, 2008 in a Valentine's Day striptease act at the Crazy Horse cabaret in Paris.

On July 9, 2008, Anderson entered the Australian Big Brother house for a three-day visit. Her appearance on this show also marked Anderson's foray into reality television with a series of her own, Pam: Girl on the Loose, which debuted on August 3, 2008 on E! in the United States.

In December 2009, Anderson guest-starred as Genie of the Lamp in the pantomime Aladdin at the New Wimbledon Theatre in Wimbledon, south-west London, England. Anderson took over the role from comedienne Ruby Wax, with former EastEnders actress Anita Dobson and comedian Paul O'Grady also booked for the role.

Pamela Anderson has also campaigned against seal hunting in Canada. In March 2006, Anderson asked to speak to Prime Minister Stephen Harper about the annual seal hunt but she was refused. In May 2006, she petitioned random individuals on the street for their opinion on the Canadian Seal Hunt. In December, 2009, Anderson, photographed in a t-shirt with a drawn picture of a seal pup on it, was featured in a new ad campaign for PETA. She appears next to the headline "Save the Seals" in the ad and urges the public to help end "Canada's annual seal slaughter."

Anderson joined forces with PETA in a campaign for the boycott of fruit-juice maker POM. The "Pom Horrible Campaign" has resulted in the company halting animal tests.

In March 2005, Anderson became a spokesmodel for MAC Cosmetics's MAC AIDS Fund, which helped people affected by AIDS and HIV. After becoming the official spokesmodel, Anderson raised money during events in Toronto, Tokyo, Dublin, and Athens.

Anderson became the celebrity spokesperson for the American Liver Foundation, and served as the Grand Marshal of the SOS motorcycle ride fundraiser.

She wrote an open letter to President Barack Obama urging the legalization of marijuana.