Engineered organisms, such as bacteria engineered through molecular biology techniques to produce antibiotics or insulin, show that biological systems can be harnessed for human purposes. Friedland et al. report the creation of two synthetic genetic systems engineered into Escherichia coli that “count” the occurrence of input signals (see Perspective by Smolke). In the first system, the authors coupled transcriptional modules to translational regulation by a trans-acting RNA that is dependent on the input signal to create systems that count up to three. In the second system, the authors engineered units encoding DNA recombinase and an inverted promoter. The recombinases are produced in response to the pulses of the input signal such that the activity of the first recombinase reorients the promoter for the second recombinase, and so on, allowing these systems to “remember” each input and only generate the final response (production of green fluorescent protein) after the required number of input signals. Both systems are flexible and, in principle, could be expanded to count past three. Applications of synthetic biological counters include programming a cell to die after so many divisions as a safety mechanism for cells used in biosensing, bioremediation, or medical applications.