His philanthropy, which began in the 1970s and paralleled his business career, expanded in 1982 with the establishment of the Milken Family Foundation. When the coronavirus pandemic swept the world in 2020, Mike drew on his five decades of working with leaders in public health and medical research to redirect the efforts of his foundations and the Milken Institute in several areas: connecting industry, public health schools and government agencies to expedite treatments and address shortages; provide policy recommendations; and disseminate accurate information.

Mike is chairman of the Milken Institute, an economic think tank whose annual Global Conference brings more than 5,000 leaders from 50 nations to Los Angeles. Other annual conferences are held in London, Washington, D.C, Singapore and the Middle East. The Milken Institute School of Public Health at George Washington University was renamed in recognition of a gift from the Institute.

Mike graduated from Berkeley with highest honors and earned his MBA at the Wharton School, where he was a Joseph Wharton fellow. He and his wife, Lori, who are members of the Giving Pledge, have been married since 1968. They have three children and 10 grandchildren.