Newcastle disease (ND) is a contagious disease of birds that can have severe economic consequences for poultry producers, including a serious impact on the international trade of poultry and eggs. Newcastle disease virus (NDV) isolates are also called avian paramyxovirus serotype-1 isolates, but only infection with virulent NDV (vNDV) causes the disease. Virulent Newcastle disease virus (vNDV) isolates are distributed worldwide and have a high capacity to mutate, allowing the development of multiple vNDV genotypes evolving simultaneously at different locations. Large gaps in existing knowledge in the areas of epidemiology and evolution limit the possibilities to control the disease. Recurrent infection of poultry and wild birds allows the maintenance of a reservoir for the viruses; however, the role of wild birds and poultry in vNDV evolution is largely unknown. In the area of diagnostics, the performance of fast and accurate diagnostics methods is often affected by the evolution of viral genomes. Therefore, there is a need for the validation of multiple recently developed experimental tests and a need to develop additional fast and inexpensive diagnostic tests to be used in the field. In the area of vaccination, the development of inexpensive thermostable NDV vaccines and the development of vaccines capable of preventing viral replication are the highest priorities for endemic countries. In countries considered free of vNDV the development of low- cost vaccines that produce minimal vaccine reactions to prevent decreased productivity are higher priorities. Worldwide, better strategies that replace the culling of infected birds are needed to control outbreaks.