He was known for photographing celebrities and royalty including Elizabeth II, Diana, Princess of Wales, Oprah Winfrey, Robert De Niro and Melanie Griffith.

During the United States invasion of Panama, De Molina was one of the first photographers present and took photos of the inside of Manuel Noriega's house.

[10][11] He made appearances on shows like Sábado Gigante, and in 1998 became the co-host of El Gordo y la Flaca, alongside Lili Estefan.

He has continued to host the show ever since, which has more viewers on its time slot than ABC, CBS, NBC and FOX combined.

[12] He has hosted and reported for programs such as Primer Impacto, Ocurrió Así, Hola América, and Club Telemundo, as well as primetime specials and his own productions.

[13] De Molina has also covered live events such as the Latin Grammy Awards in Las Vegas,[14] and the New Year's Eve celebration in Times Square, Manhattan.

[15][16] While in South Africa to cover the 2010 FIFA World Cup, Molina was stranded during a safari when his car engine caught fire, and he was surrounded by lions.

[19] In October 2008, Random House published his second book La Dieta del Gordo about his own struggles with weight, and his secret to losing 70 pounds.

[32] He has also cultivated a collection of art and photography, which includes works by Hunt Slonem, José Bedia Valdés, Li Hongbo, Liu Bolin, Valérie Belin, Lalla Essaydi, Manuel Mendive and Jean-François Rauzier [fr].

[2] De Molina serves on Art Basel's host committee, and his annual party is regarded as the unofficial "kick-off" event of the international exhibition show.

His personal car collection includes a special edition 2013 Mini Cooper GP, Mercedes-Benz SLS AMG and a 2006 Ford GT40.