The New York State Department of Health has conducted a number of studies over the past 10 years investigating health impacts related to the September 11, 2001 (9/11) disaster among New York City residents and New York State World Trade Center (WTC) responders. Efforts to evaluate the health effects of WTC exposures in these cohorts presented numerous challenges, including study design and associated concerns about bias, identifying the affected populations, gaining community support and participation, and determining the most appropriate clinical testing and follow-up approaches. The unique position of a state public health agency provided multiple points of support for these efforts. An overview of what was found and the lessons learned during the response to the 9/11 disaster is presented, from the viewpoint of a state public health agency.