Holmes' designer accomplishments stem from a career as an international model. Holmes worked for Dior, Dolce & Gabbana, Valentino, Chanel, Versace, John Galliano, Christian Lacroix, Herve Leger, Badgley Mischka, Nicole Miller, Marc Jacobs, and Prada. Holmes also has appeared in ad campaigns for Yves Saint Laurent, Fendi, Escada, Guess, Revlon, Karl Lagerfeld, Louis Vuitton, and Victoria's Secret. Holmes was in television commercials for Peugeot (which actually won an award and was filmed by Madonna videographer Jean-Baptiste Mondino). She then followed with two more commercials, for Triumph and H&M lingerie. Susan then starred as "the runaway bride" alongside fellow models Tyra Banks, Kate Moss, and Helena Christensen in the British film Inferno! She has appeared on the covers of Vogue, Elle, Marie Claire, Playboy and Australian Maxim.

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