The requirements of gene therapy for cancer are distinct from those of gene therapy for hereditary monogenic diseases. In cancer the aim is to kill, not cure tumour cells. Also issues such as duration of gene expression and immunogenicity of vector systems are of less relevance than efficiency of delivery to all tumour cells. In this light, we discuss the vector systems currently available and the methods to target transgenes to tumour cells. In view of the current limitations in both vector systems and targeting of tumours, we discuss the strategies that may be applied to increase the effectiveness of inefficient delivery, such as immune activation, bystander cytotoxicity and replication-competent viruses.