Live attenuated, cold-adapted influenza vaccines exhibit several desirable characteristics, including the induction of systemic, mucosal, and cell-mediated immunity resulting in breadth of protection, ease of administration, and yield. Seasonal live attenuated influenza vaccines (LAIVs) were developed in the United States and Russia and have been used in several countries. In the last decade, following the incorporation of the 2009 pandemic H1N1 strain, the performance of both LAIVs has been variable and the U.S.-backbone LAIV was less effective than the corresponding inactivated influenza vaccines. The cause appears to be reduced replicative fitness of some H1N1pdm09 viruses, indicating a need for careful selection of strains included in multivalent LAIV formulations. Assays are now being implemented to select optimal strains. An improved understanding of the determinants of replicative fitness of vaccine strains and of vaccine effectiveness of LAIVs is needed for public health systems to take full advantage of these valuable vaccines.