The viruses of the Paramyxoviridae family are enveloped negative-stranded RNA viruses comprising several important human pathogens, including parainfluenza, measles, mumps and respiratory syncytial viruses. To date, most of the information on the molecular mechanisms of replication and transcription of Paramyxoviridae has been derived from studies conducted on Sendai virus. The continuous development of new strategies to manipulate genomes of negative-stranded RNA viruses genetically, provides new tools to study the structure-function relationships of the viral components and their contribution to pathogenicity. The improvement of molecular and cellular biology techniques allows to characterize extensively purified viral proteins and to elucidate both the nature and the role of their interactions with host cell proteins. We herein focus on the state of the art on the molecular mechanisms of transcription and replication of Paramyxoviridae. We conclude on the therapeutical perspectives and the advancements which are expected to arise in the future from structural and molecular studies.