The Experimental Biology 2012 meeting in San Diego, CA, included events to celebrate the 125th anniversary of the founding of the American Physiological Society (APS) and reflect on the recent accomplishments of the society. Most of the APS activities in the past quarter century were guided by a series of strategic plans. Membership in the APS increased by 76% since 1987, and there are now 8,342 regular members of the society, including an expansion of international members to 26% of APS's membership. The numbers of elected officers and committee members have expanded to accommodate this larger membership. APS Publications changed dramatically during this time, having adopted online submission and review of manuscripts as well as a streamlined review and publications process that have significantly shortened the period from submission to acceptance to publication. Compared with 1987, the number of manuscripts submitted has increased by 80% and the number of printed pages increased by 52%. In addition to the refinement of the Experimental Biology meeting (Federation of American Societies for Experimental Biology meeting before 1993) format, APS launched a specialty conference program in the 1990s. The educational offerings of APS also dramatically expanded in the past 25 yr, often supported by external grants and contracts. APS education programs now support physiology education and science awareness at K-12, undergraduate, graduate, and professional levels as well as continuing education of its members. The founding of APS was tied to the need for effective advocacy, and APS continues to meet those goals through its Science Policy Committee and Animal Care and Experimentation Committees. At its 125th birthday, APS continues to serve the discipline and the needs of its membership. (Contains 2 tables and 2 figures.)