Vaccines are a cornerstone in any pandemic influenza preparedness plan. Successful supplementary mass vaccination programs require proper advance planning. We aimed to identify general, and Israeli specific, challenges and opportunities before initiating the Israeli pandemic influenza vaccination program in order to better plan implementation of the program. Following the vaccination campaign the analysis was retrospectively examined in order to determine whether the challenges were properly identified and whether the opportunities were indeed realized. The major challenges identified were prioritization; ongoing communication with the public; balancing between central management and accessibility; and preventing vaccination errors. The major opportunity was expected to be the chance to enhance cooperation and communication between different organizations both within and outside of the health system at local, national and international levels. The vaccination program was planned based on this analysis. In retrospect, the analysis identified the key challenges and opportunities and appropriate measures were taken. However, the criticalness of acceptance of the vaccine among health care practitioners was not given sufficient attention and should be addressed in future vaccination programs. Analysis of global and local challenges and opportunities served as a useful tool for planning a pandemic influenza vaccination program. Lessons learned from this analysis could serve to foster cooperation and communication between various agencies in the event of planning rapid mass vaccination programs as well as for more routine public health vaccination campaigns.