There are many challenges facing researchers with projects requiring multicentred ethics approval. Achieving ethical approval at multiple sites, whether statewide or nationally, is a complex and time-consuming experience, compounded by the research process itself, as well as the recruitment of clinical sites and participants. Human ethics and research committees act as research gatekeepers and, as many research activities involve multiple applications and multiple approvals, can considerably delay the commencement of a project. A delay in ethics approval results in delays recruiting staff and participants, delays in the utilization of funding, and in delays regarding the progress and completion of projects. Such problems are additional problems for researchers of vulnerable populations, such as those in mental health or palliative care, where multicentred research is necessary to ensure the validity of the project itself. A current example of work that has required multicentred human ethics and research approval from around Australia is the establishment of the National Register of Antipsychotic Medication in Pregnancy. The guidelines for embarking on such a project with the requirement of multicentred ethical approval are described. Some of the issues, recommendations, and guidelines presented by the authors are taken from their experiences in establishing multicentred research projects.