There is a clear need for new, selective, cancer treatments that do not cause the cross-resistance which occurs with currently available chemotherapeutic agents. Gene therapy is a promising approach, but to date, it has shown limited effectiveness in clinical trials because of insufficient gene transduction. Many investigators are now revisiting the 'old' idea of using tumour-specific, replication-selective viruses or bacteria to treat cancer. These agents can be directly oncolytic, but can also be used to simultaneously express therapeutic genes in target cells or induce tumour-specific, cell-mediated immunity. We discuss the promise of this rapidly evolving field and examine the potential barriers to its success.