The fall 2009 campaign to vaccinate high-risk U.S. residents against the 2009 H1N1 influenza virus presented three key challenges that had significant impact on the effectiveness of campaigns conducted by local health departments (LHDs), schools, and other community partners. These issues included those of communication and trust, both between partners and with the public; the ethics and practicalities of getting vaccine to those at highest risk; and the planning and execution of large-scale, school-located vaccination (SLV) clinics. Approaches to address these challenges and build sustainable local partnerships between schools and LHDs are explored.