Recent European Union (EU) regulations have been introduced to discourage the capture of undersized specimens with the aim of reducing the bycatch mortality imposed by commercial fisheries. We argue that we still lack accurate data regarding basic information required to properly implement these regulations for most Mediterranean ecosystems, including the true mortality imposed by fisheries, escape rates from fishing gears and the capability of specimens to survive following discard. We suggest that additional reliance on physiological biomarkers could assist in all aspects of the data collection required to support implementation of the EU discard ban (aka landing obligation), particularly in determining which species should receive special dispensation from this policy. Ideally, this new approach, here termed the ‘Fisheries Environmental and Physiological Stress Analysis’ (FEPSA), would become an important step for any fish stock assessment within the ecosystem approach to fisheries management and the recognition of Good Environmental Status, as established by the EU in the Marine Strategy Framework Directive (2008/56/EC). In particular, the main goal of FEPSA would be applying the study of physiological stressors to exploited stocks to estimate the so-called collateral fishing mortality, which includes the mortality experienced by fish that escape after interacting with fishing gears or that are discarded, with some degree of injury or physiological stress. The approach outlined here, which is described for bottom trawls but adaptable to any other type of fishing gear, is not a trivial undertaking but is a requirement for collecting the data required by recent EU fisheries policies. While we agree that the threats to marine biodiversity posed by fishing and associated discard practices require strong policy interventions, we emphasize that the research programs needed to support such initiatives, including the landing obligation, should be given equal priority. This is particularly true for Mediterranean fisheries, which are at a complex intersection of jurisdictional boundaries, numerous additional ecosystem threats including widespread pollution, thermal variation and hypoxia, and are historically understudied as compared to fisheries and species in more northern climates.