In June this year, the tetracycline-regulated gene expression system (tet system) celebrated its tenth "birthday". In the past ten years a continuous stream of changes made to the tet system's basic components has led to a remarkable improvement in its overall performance. It was not until this year, however, that the full benefits of these improvements became apparent. In particular, usage of the tet system is no longer limited to immortalized cell lines and transgenic animals. In this review, we will describe the obstacles encountered in delivering the tet system's components to primary cells and tissues as well as the methods now used to overcome them. We will also focus on a novel system that is conceptually similar but based on different antibiotic/transcription factor pairs.