"Your happiness grows in direct proportion to your acceptance and in inverse proportion to your expectations," Fox told ABC News' Diane Sawyer. "Acceptance doesn't really mean you're resigned to it. It just means acknowledging that that's what it is."
The actor and head of the Michael J. Fox Foundation for Parkinson's Research recently traveled around the world and sought out people from all walks of life, searching for the answer to one question.
Are some people just more optimistic than others? And if so, why?
Fox, 47, began his journey with a visit to Lance Armstrong's home in Texas, where he sat down with the seven-time Tour de France winner to discuss what keeps him striving. Armstrong's struggle with cancer that spread to four parts of his body led him to start LiveStrong, a foundation that offers support to cancer survivors.
Armstrong credits much of his own success on the bike to his battle with cancer.
"I don't think it's a stretch to say that none of, none of my success on the bike would have been possible without that disease," he said. "Life wouldn't have been necessarily empty, but it would not have looked like this."
Armstrong also said his optimism is inspired by his mother, who overcame her own set of challenges as a teen mom.
"I give all the credit to my mom," he said. "She's really a survivor. She's as strong and tough as they come and she never looks at anything in a negative light."
Fox sees a parallel between himself and Armstrong, because both grappled with illness as young men and both draw strength from their families. Fox's wife, actress Tracy Pollan, 48, has stood by him through the years, even though she hesitates to call herself as great an optimist as her husband.
"It goes against my natural grain," she joked.
It seems that happiness does come naturally to some people.
Fox said he found "the most relentlessly cheerful guy you've ever met" outside a New York City subway.
Oscar Smith Jr. works two jobs, including one handing out free newspapers on a street corner. Every weekday, rain or shine, Smith greets commuters with a huge smile and a boisterous "good morning" -- and people can't seem to help but smile right back.
Fox donned a smock and grabbed an armful of newspapers to find out exactly what it is about Smith that makes him so happy.
"It has to come from within," Smith said. "To start a day with a smile and just saying say hello, you know, the eye-to-eye contact, it just helps people so much."
"Just by saying, 'Good morning, how are you?' You can see sort of the lights go on in ... in people's eyes, and their faces light up," Fox told Sawyer. "And again, it's about the connections."
Fox's pursuit of happiness took him to Washington, D.C., for the inauguration of President Barack Obama, and also took him across the globe, to one of the happiest places on Earth. In Bhutan, in the Himalayas, they measure "gross national happiness."
"I spoke to the minister of development," Fox told Sawyer. "He's also called Detector of Gross National Happiness.