Live attenuated vaccines have been used for the prevention of a large number of virus infections, including those caused by paramyxoviruses. Despite their long and successful history the nature of the attenuating mutations in these viruses is not known. Paramyxoviruses are responsible for a number of common diseases particularly in young children and of these respiratory syncytial virus is recognised as a major problem. The development of a reverse genetics system for human respiratory syncytial virus has enabled the construction of recombinant viruses. Coupled with the technology to sequence complete genomes of attenuated vaccine candidates, this has led to rapid progress in the identification of the mutations responsible for the attenuated phenotype, and in the rational design of attenuated vaccines for this important human pathogen.