<p>This paper presents the first comprehensive review of the occurrence of pharmaceuticals in natural aquatic environments in Australia. A total of 24 peer-reviewed studies and one regional survey were examined. Across these studies, 122 active pharmaceutical ingredients (APIs) from various therapeutic classes were quantitatively detected in Australian aquatic environments. Additionally, 20 APIs were tentatively identified using non-targeted analytical methods. The most frequently detected therapeutic classes were antibiotics, psycholeptics, and antidepressants. Surface waters are the most extensively studied aquatic matrix in Australia, while data on other aquatic environments remain limited. In most cases, detected API concentrations were low and comparable to global levels; however, some biota concentrations exceeded values previously reported internationally. The available data predominantly represents highly populated areas along Australia’s east coast. A screening-level environmental risk assessment of maximum surface water concentrations suggests that 21 APIs may pose a potential risk to aquatic ecosystems. This accounts for almost one-third of the APIs for which risk quotients could be calculated. Significant data gaps remain. Only a fraction of all available APIs have been tested for within Australian aquatic environments, and metabolites remain largely understudied. Increased monitoring and occurrence data are needed to better assess environmental risks. This review highlights key priorities for advancing research, monitoring, and management of APIs in Australian aquatic environments.</p>