The Milk star was still reeling from his marriage split from actress Robin Wright when his teenage son Hopper suffered a devastating skateboarding accident, which left him in need of emergency brain surgery.
In the days that followed, Penn watched him make a full recovery with the help of pain medication, and the actor reveals as soon as the tremendous tremor hit Haiti, he couldn't bear the thought of survivors undergoing amputations without the same medical help his son had received.
He tells the New York Times, "I had been single-parenting after a divorce for about eight months, and in that time my son had a traumatic head injury. And after getting through the life threat or the brain-damage threat, still there was the pain, and then he was given morphine for the pain, and I guess... I really found affection for what those pain medications could do to people.
"I had just seen his relief and so then it was four days before the earthquake that both he and his mother had found they were ready to spend some time together, so he left, which was initially kind of a 24/7 burden of eight months that I needed to break through... After that I was just sitting around missing him, and the earthquake happened.
"I was hearing about the amputations and so on without any IV (intravenous) pain medications, so I put a little group together, but the intention initially was just to go down and distribute those medications to the hospitals and clinics that were doing surgeries. And then we had a pretty good group of people, and there were gaps to be filled... One commitment built into another one."
Penn founded the J/P Haitian Relief Organization and two years later he's still a very present force in Haiti as both aid worker and activist.