Mediterranean coastal lagoons provide important ecological functions and nature’s contribution to people, but they are particularly vulnerable to multiple pressures due to their location at the land-sea interface and the many activities they host. Numerous research and monitoring programs have been conducted to study the functioning of Mediterranean coastal lagoons and to improve their ecological and chemical status, especially since the 2000s with the EU Water Framework Directive. However, many coastal lagoons still had not achieved a good ecological status by 2018. The soft-bottom benthic ecosystem plays a crucial role in the functioning of shallow coastal lagoons, regulating among others nutrient and oxygen fluxes, and hosting a high biodiversity. The alteration of this compartment by anthropogenic pressures is therefore a major problem. Through a literature review, this paper aims to summarize information available on the impacts of the five main human-induced pressures — i.e. exploitation of natural resources, habitat destruction, climate change, pollution and alien invasive species — on the soft-bottom benthic ecosystem in Mediterranean coastal lagoons (period 2000—2022), and to identify perspectives for future research that can contribute to the improvement of monitoring programs. Our review shows that resource exploitation and nutrient pollution have been the two most studied pressures whereas research is still underdeveloped on the impacts of climate change, invasive alien species, and contaminants of emerging concern. We also found that the recording and quantification of pressures is still poor, and that their cumulative effect is poorly understood. In terms of indicators, the microbial and microphytobenthic compartments are being overlooked and functional approaches could be strengthened. This review could help scientists realign research on pressures of priority interest and thus better assist stakeholders in managing coastal lagoons in times of global change