Replication-competent vectors are derived from attenuated viruses whose genes, that are nonessential for replication in cultured cells in vitro, are either mutated or deleted. The removal of one or more nonessential genes may reduce pathogenicity without requiring a cell line to complement growth. Herpes simplex viruses (HSV) are potential vectors for several applications in human healthcare. These include delivery and expression of human genes to cells of the nervous systems, selective destruction of cancer cells, prophylaxis against infection with HSV or other infectious diseases, and targeted infection to specific tissues or organs. This review highlights the progress in creating attenuated genetically engineered HSV vectors.