The inability to reliably express foreign proteins in postmitotic neurons has hampered numerous studies in the field of neurobiology. Within the past several years, a number of viral vectors that overcome this problem under controlled conditions in vitro have been developed. In particular, recombinant adenoviruses have proved to be efficient, non-cytotoxic vectors for manipulating neurons in dissociated and organotypic cultures, when used at low viral titres. In contrast, vectors derived from herpes simplex virus 1 still suffer from concerns regarding cellular cytotoxicity, in spite of several generations of vector development; however, recent advances in amplicon technology may solve this problem. Finally, several new-generation vectors, including those generated from adeno-associated virus, show great promise as neuronal gene-transfer vectors in vivo.