L.S. Skaggs is the former chairman of American Stores Company, a supermarket and drug store holding company that grew under his direction from 11 stores to become the largest combined supermarket/drug store chain in the United States, owning Jewels Food Stores, Savon-Drugs, Star markets, Acme Markets, Osco Drug, and Lucky Stores. In 1999, American Stores was sold to Albertson's, Inc., a grocery store chain whose original founders included Skaggs father.

L.S. and Aline W. Skaggs' philanthropy supports Catholic education, scientific research, basic human needs, and wildlife preservation. The Skaggs Institute for Research, a charitable foundation created by the Skaggs in 1996, is TSRI's largest benefactor and to date has provided grants of more than $75 million to fund TSRI's renowned Skaggs Institute for Chemical Biology, as well as graduate, postdoctoral, and clinical research programs. Three principal investigators at the Skaggs Institute are Nobel Prize laureates.

In addition to their support of TSRI, the Skaggs have funded major education projects in the Diocese of San Diego and Archdiocese of Los Angeles, and contributed to the Scripps Clinic in La Jolla. Nationally, they have provided funds to build a Catholic elementary school and high school near Salt Lake City, to create a medical clinic at Harvard University, and to provide thousands of scholarships to pharmacy students and disadvantaged youth.