Naturally existing Newcastle disease virus (NDV) can specifically execute oncolytic ability in clinical studies. Reports from clinical trials using NDV as oncolytic agents showed promise and warrant results in cancer therapy. In recent years, reverse genetics technology has been used widely in the studies of NDV virology. More recently, the technology was applied to optimize the oncolytic efficacy of NDV, for instance, modification of the F gene, and expression of GM-CSF, IFN-γ, IL-2 or TNF-α. NDV is widely investigated in cancer therapy and will definitely offer a prosperous future for clinical cancer therapeutics. We reviewed the developments of cancer therapy by recombinant NDV using reverse genetics technology, as well as our own experience in this domain.