The Hollywood stars are making the trek with Foster The People frontman Mark Foster and singer Kenna, who organised the Summit On The Summit: Kilimanjaro climb up Africa's tallest peak.
On Thursday (03Jan12), the hikers arrived in Tanzania ahead of their gruelling seven-day, 50-mile (80-kilometre) journey up Kilimanjaro.
The stars will use social media to draw attention to the problem of water-borne illness and disease, and will be supported by actresses/activists Olivia Wilde and Dianna Agron as they blog about the mission online.
Glee star Agron has tweeted, "Good luck Kenna & everyone on Summit On The Summit 2! So sad that I couldn't make this climb!! I am sending my love & support from over here!!"
Jessica Biel, Emile Hirsch, Isabel Lucas and rapper Lupe Fiasco joined Kenna on his first celebrity Summit adventure in 2010.