The depletion of traditional oil fields is driving the oil & gas industry to explore new exploitation sites previously considered as unprofitable. Deep-sea oil fields represent one of these new areas of exploitation. Well drilling during exploration and production operations generate large quantities of drilling waste whose biological impact on the deep-sea floor remains largely unknown. Because of the harsh abiotic factors characterizing this environment, the evaluation of this impact remains challenging. High hydrostatic pressure is the prominent factor which will affect in-situ biological processes. This review will examine the feedback on the various strategies used to evaluate the biological impact of deep-sea drilling waste deposition as well as the current technological limitations. Given the complexity of this issue, a good perspective strategy would be to trend towards the research and development of more relevant bioassays, especially considering the crucial factor of hydrostatic pressure.