Interpreting signals coming from the surrounding environment and responding to these stimuli by adjusting physical or metabolic state is the most fundamental ability of living organisms. Repurposing these natural abilities for the detection and responding to different molecules is one of the key focuses of synthetic biology because the overall strategy could provide advanced solutions for different diseases. Also by being naturally suitable to the design-build-test-learn manner of synthetic biology, biosensors are great examples of what engineering and biology could achieve when they come together. Literature has many examples of intellectually designed biosensor systems, which may overachieve and outperform existing technologies with a completely biocompatible structure. In this chapter, design and application of these biosensor systems will be investigated.