Yeast cells can be utilized as whole-cell biosensors for the detection of an array of target analytes. This technology is derived from the latest molecular biology techniques enabling the modification of the yeast genome to enhance the cells’ metabolic properties. Current methods to produce correctly folded recombinant proteins, particularly receptors in yeast, are now highly successful, and the implementation of diverse reporting strategies is well documented. A myriad of yeast whole-cell biosensors are now utilized in various laboratories, and some are also commercially available. A major target of these biosensors is endocrine disruptors, a class of organic molecules that can disturb the vertebrate endocrine system and therefore pose a potential threat to the environment. Recent studies focused on building new biosensors using receptors such as G-protein-coupled receptors and the thyroid receptor. In this chapter, we will present a selection of newly developed biosensors and the diverse reporting strategies used to transduce the binding event into a measurable signal.