"If you can have the light shine on something, if you show up to something, then it makes it all worthwhile," Margulies told ET.
The 48-year-old actress had a close friend, Jenifer Estess, diagnosed with ALS back when she was on ER. At the time she rallied her TV co-stars to show their support for Project A.L.S.
"The first event I went to, I was dragging all my co-stars: George Clooney, Noah Wyle," Margulies said. "And then the next year, it was Brad Pitt and Jennifer Aniston and the cast of Friends. It was quite remarkable."
ALS, also called Lou Gehrig's disease, is a disease of the nervous system that weakens muscles and impacts physical function. According to the Project A.L.S. website, the organization "recruits the world's best scientists and doctors to work together -- rationally and aggressively -- toward a better understanding of the ALS disease process and, in parallel, better therapeutic strategies."
ET's Nancy O'Dell has seen what the destruction the disease can cause, as she lost her beautiful mother Betty to ALS in 2008.
"When it happens in your circle, then people seem to call to action," Margulies said. "Everyone's vulnerable, and you can't give up."