The platypus (Ornithorhynchus anatinus) is one of the world’s most evolutionarily distinct mammals, one of five extant species of egg-laying mammals, and the only living species within the family Ornithorhynchidae. Modern platypuses are endemic to eastern mainland Australia, Tasmania, and adjacent King Island, with a small introduced population on Kangaroo Island, South Australia, and are widely distributed in permanent river systems from tropical to alpine environments. Accumulating knowledge and technological advancements have provided insights into many aspects of its evolutionary history and biology but have also raised concern about significant knowledge gaps surrounding distribution, population sizes, and trends. The platypus’ distribution coincides with many of Australia’s major threatening processes, including highly regulated and disrupted rivers, intensive habitat destruction, and fragmentation, and they were extensively hunted for their fur until the early 20th century. Emerging evidence of local population declines and extinctions identifies that ecological thresholds have been crossed in some populations and, if threats are not addressed, the species will continue to decline. In 2016, the IUCN Red Listing for the platypus was elevated to “Near Threatened,” but the platypus remains unlisted on threatened species schedules of any Australian state, apart from South Australia, or nationally. In this synthesis, we review the evolutionary history, genetics, biology, and ecology of this extraordinary mammal and highlight prevailing threats. We also outline future research directions and challenges that need to be met to help conserve the species.