Synthetic biology promises to enable the design of therapeutics and devices based on modular genetically encoded components, but the number of interoperable parts and circuits remains limited. Now two groups have added much needed parts to realize the potential of precision engineering circuits in human cells. Khalil et al. use artificial zinc finger domains, which can be readily engineered to recognize various target DNA sequences, as the basis for a modular, customizable set of synthetic transcription factors (sTFs) and demonstrate how to build and tune these sTFs for higher-order synthetic gene circuits in yeast, a useful testing ground for circuits that might help bridge to studies in human cells. A second group, Wei et al., exploit a family of bacterial pathogen proteins known as effectors that can modulate host cell signaling and dampen immune responses. They use effectors to selectively modulate mitogen-activated, protein kinase–regulated signaling pathways, including those responding to osmolarity in yeast, and show that these effectors can be used to reshape signaling input and output behavior. They use the same effectors as a switch to toggle on and off the activity of human CD4+ T cells in response to a simple drug signal. Control switches like these might find application in adoptive immunotherapy. (Cell 150, 647–658, 2012; Nature 488, 384–388, 2012)