Recently we have perfected a chemical-genetic approach to gain precise spatio-temporal control of cellular signaling. This approach entails the cell-type specific expression of mutant G-protein coupled receptors which have been evolved to be activated by the pharmacologically inert drug-like small molecule clozapine N-oxide. We have named these mutant GPCRs DREADDs (Designer Receptors Exclusively Activated by Designer Drugs). In this paper we will first review recent applications of this technology for the remote control of neuronal and non-neuronal signaling. Next, we will also introduce new variants which could be useful for the control of cellular signaling in discrete cellular compartments. Finally, we will suggest future basic science and therapeutic applications of this general technology.