Biased signaling is a natural result of GPCR allosteric function and should be expected from any and all synthetic agonists. Therefore, it may be encountered in all agonist discovery projects and must be considered as a beneficial (or possible detrimental) feature of new candidate molecules. While bias is easily detected , the synoptic nature of GPCR signaling makes translation of simple in vitro bias to complex in vivo systems problematic. The practical outcome of this is a difficulty in predicting the therapeutic value of biased signaling due to the failure of translation of identified biased signaling to in vivo agonism. This is discussed in this review as well as some new ways forward to improve this translation process and better exploit this powerful pharmacologic activity.