Background and Purpose: The Sonic Hedgehog (SHH) signaling pathway is a key regulator of embryonic development and its disruption is implicated in birth defects, including the most common structural human birth defect orofacial clefting (OFCs). Chemicals can interact with the SHH pathway at multiple molecular targets along the signaling cascade involved in both Hh secretion and sensing. Exposure during critical windows during and after organogenesis can lead to OFCs. To organize the state of evidence linking SHH disruption to OFCs in an opensource and regulatory relevant manner we are developing an Adverse Outcome Pathway (AOP) network in the AOP wiki framework. Methods: This AOP Network is being developed through the OECD’s AOP development program (EAGMST workplan project 1.101.). We have proposed the development of six AOPs with molecular initiating events (MIEs) spanning the known molecular targets of disruption including SHH ligand modification with cholesterol and palmitoylate, ligand secretion, mesenchymal reception, and signal transduction. We have applied a systematic literature search and review to assemble data for each key event relationship (KER) in the pathway. Search results were screened for relevance of title/abstract and and those that passed were reviewed in full to determine their applicability for the KER. Each KER includes a table of relevant search information (date, search terms, citations, etc) and weight of evidence (WoE) assessments were performed in accordance with OECD AOP development guidelines. Results: To date, three of the six AOPs are actively underdevelopment in the AOP wiki (AOPs 460, 491, 502). We have completed AOP 460: Antagonism of Smoothened receptor leading to orofacial clefting in the wiki and are preparing to submit for scientific review and publication. Our development has helped to identify multiple data gaps, namely the lack of dose response and time course studies linking the downstream KERs. We have found that the majority of evidence exists for the nonadjacent relationship linking the MIE with OFC. Through the development of this network we have experienced the challenge common to complex AOP networks that KERs are often not well captured in a simple graphical format. This is especially true for nonadjacent relationships which we have found often hold the highest WoE and most experimental data. It is hoped that further studies will be performed to increase the WoE for this pathway. Conclusions: The intended use of this AOP network from a regulatory standpoint is to improve predictive potential of developmental hazards as they relate to the SHH pathway and OFCs. It is hoped that this AOP network can be applied to data from in silico and in vitro high-throughput screening assays (HTS) to guide selection of agents for further investigation in more representative models of orofacial development. Disruption of the Sonic Hedgehog pathway has broader outcomes than just OFCs and SHH is known to play a role in many aspects of embryonic development including patterning of many systems and limb and digit development. This network can be used as part of an integrated assessment of toxicity and can help to guide risk assessment for potential exposures during development