At present there is no consistent approach for the definition of Good Environmental Status (GES) and targets in the Mediterranean Sea, especially for Biodiversity Descriptors, according to the Article 12 of the Marine Strategy Framework Directive (MSFD). The use of plankton indicators in the Mediterranean Sea refers mostly to pelagic habitats in coastal waters and to case studies connected with environmental pressures, e.g. in the Adriatic, Aegean etc. The aim of this review is to study the existing biodiversity indicators for different plankton groups in order to compare GES definitions for the Biodiversity Descriptor and identify the relevant gaps and priority needs to improve coherence for the MSFD implementation across the Mediterranean. For these purposes, we focus on plankton indicators for phytoplankton, zooplankton and prokaryotes. Regional conventions (OSPAR, HELCOM, Barcelona and Bucharest Conventions) have long considered phytoplankton as a key element for integrated assessment systems. Phytoplankton biomass, community composition, abundance, frequency and intensity of blooms are used for such assessment purposes. Chlorophyll a still remains the most widely used indicator mostly thanks to its time saving, cost-effective and reproducible analytical methods that provide easily comparable datasets. Despite some integrated indices proposed for phytoplankton in the literature at the Mediterranean level, a number of constrains still prevent their wide use. Regarding zooplankton communities, commonly used indicators have a taxonomic base while recently size structure and biomass can provide a valuable index of zooplankton population dynamics and ecosystem production. Jellyfish blooms’ occurrence and frequency are also considered important zooplankton indicators in specific areas, e.g. North Adriatic. Concerning the prokaryotes, so far MSFD takes into account only their pathogenic component. The revision of MSFD GES definitions shows that all Mediterranean MSs have defined GES at the Descriptor level (e.g. D1 Biodiversity), but our comparison of approaches shows a low level of coherence in GES related to pelagic habitats and plankton communities. Gaps mostly focus on the lack of thresholds and baselines for many biodiversity indicators, and on the scarcity of common and consistent methodological approaches for biodiversity assessment by the MSs. Suggestions to fill these gaps and inconsistencies among MSs include: integration of EU legislation and Regional Agreements and Conventions; targeting on priority species and habitats; testing of existing biodiversity indices with good performances in case studies; coordination and intercalibration actions for the establishment of threshold values and baselines; determination of common methodologies; undertaking of regular monitoring programs and impact assessment studies at regional and sub-regional levels.