The Antarctic Treaty has been the principal governing force in Antarctica since 1961. The Protocol on Environmental Protection to the Antarctic Treaty (Madrid Protocol) requires that all past and present work and waste-disposal sites are cleaned up unless doing so would cause greater environmental damage or the site is considered to be a monument of significant historical importance. Despite this requirement, legacy waste issues remain unresolved in parts of Antarctica. Clean-up operations in Antarctica are complicated by a combination of restricted access, extreme weather, financial limitations and logistical constraints. Further complications arise at sites such as Wilkes Station, where the requirement for clean-up coexists with the desire to preserve potentially valuable heritage items. Several buildings and artefacts with potential heritage value remain at Wilkes Station. However, Wilkes Station is not officially designated as a historic site or monument under the Antarctic Treaty, nor is it a national or world heritage place under Australian domestic legislation. Consequently the buildings and relics at Wilkes Station are afforded little protection under the existing relevant domestic and international legislative frameworks. This paper uses Wilkes Station as a case study of the complexities associated with conducting clean-up operations at contaminated sites with informal heritage value in Antarctica. The legislative and environmental considerations surrounding clean-up operations at Wilkes Station are also investigated. Furthermore, we argue the importance of a multi-disciplinary approach to operations which facilitate the clean-up of legacy waste and preservation of the potential heritage values at Wilkes. Finally, we recognise that the complexities discussed in this paper have wider applicability and we investigate the relevance of these issues to other Antarctic contaminated sites with formal or informal heritage value.