Boston University's (BU) CityLab program was created in 1991 as a partnership between faculty members of BU's School of Medicine and School of Education in response to the first call for proposals under the Science Education Partnership Awards initiative of the National Institutes of Health. CityLab's founders recognized the need for CityLab, a centrally-located facility for pre-college teachers and students to explore the burgeoning world of biotechnology. The mission has always been to share the excitement of science with students and teachers by engaging them in hands-on laboratory experiences, thereby fostering the development of a robust pool of scientists and physicians and a scientifically-literate populace. In order to reach more schools, particularly those that could not come to CityLab's facility in Boston, the CityLab team pioneered the mobile science laboratory concept with the launch of its MobileLab in 1998. Both CityLab and MobileLab have been replicated in the U.S. and abroad. CityLab has sustained itself because it has benefited from stable leadership, built and disseminated models for hands-on STEM education, embraced innovation by creating new programs to serve additional populations, and developed diverse funding streams. The CityLab program has been remarkable in its outreach, success, and longevity.