The delineation of the molecular basis of cancer allows for the possibility of specific intervention at the molecular level for therapeutic purposes. To this end, viral and nonviral vectors have been designed for delivery and expression of genes into target malignant and non-malignant cells. Gene transfer by available vectors, applied both in the ex vivo and in in vivo contexts, has resulted frequently in the desired cellular phenotypical changes. In this regard, recombinant adenoviruses have been particularly efficient for in vivo gene transfer. Importantly, numerous human clinical protocols using adenoviruses have rapidly entered Phase I clinical trials. However, major vector-related problems remain to be solved before the transfer of therapeutic genes by adenoviruses can become an effective and common place strategy for cancer. An overriding obstacle is the basic ability to deliver therapeutic genes specifically into tumor cells. Here we review a diverse number of advances in adenoviral vectors being developed for overcoming this obstacle. As vector technology fulfills these requirements for obtaining the “targetable-injectable” vector, it is anticipated that promising results already observed in pre-clinical studies will translate quickly into the clinic.