Schematic overview of a comprehensive OR assay platform and the approximate single assay compound throughput. Given the inherent complexity of the combinatorial receptor code and the remaining challenges of current in vitro OR assays, a comprehensive OR assay platform would aim to balance screening throughput and organism relevance by incorporating in vitro, ex vivo, and in vivo assays. A robust in vitro platform would enable the initial screening of thousands of odorant compounds. Agonists or antagonists identified from in vitro systems could then be screened using ex vivo OSN assays (medium throughout and relevance) or in vivo imaging assays (low throughput and high relevance). A salient benefit of in vivo over ex vivo or in vitro assays is that odorants are delivered in the vapor phase to the fully intact peripheral olfactory system (olfactory epithelium and bulb). The main benefit of ex vivo over in vitro assays is the use of OSNs as an expression system for native (i.e., untagged) receptors. OB, olfactory bulb; OE, olfactory epithelium; OSNs, olfactory sensory neurons; MU, olfactory mucus.