Computation using DNA has many advantages, including the potential for massive parallelism that allows for large number of operations per second, the direct interface between the computation process and a biological output, and the miniaturization of the computing devices to a molecular scale. In 2001, we reported on the first DNA-based, programmable finite automaton (2-symbol-2-state) capable of computing autonomously with all its hardware, software, input, and output being soluble biomolecules mixed to solution. Later, using similar principles, we developed advanced 3-symbol-3-state automata. We have also shown that real-time detection of the output signal, as well as real-time monitoring of all the computation intermediates, can be achieved by the use of surface plasmon resonance (SPR) technology. More recently, we have shown that it is possible to achieve a biologically relevant output, such as specific gene expression, by using a reporter-gene as an output-readout. We cloned the input into circular plasmids, and thereby achieved control over gene expression by a programmable sequence of computation events. Further efforts are currently directed to immobilization of the input molecules onto a solid chip to enable parallel computation, where the location of the input on the chip represents specific tagging.