The design and construction of synthetic gene circuits with complex spatiotemporal dynamics was pioneered in bacteria, but it took almost a decade until synthetic biologists were able to construct genetic circuits with complex spatiotemporal dynamics in mammalian cells. This review highlights the most recent advances in mammalian synthetic biology, and it describes metabolite, hormone, and light-triggered genetic switches as well as the design and construction of synthetic networks that feature tunable oscillations. We conclude by discussing not only the current limitations but also possible ways to transform the construction of synthetic mammalian systems from an art into a predictive engineering discipline. © 2010 Elsevier Ltd.