AbstractThe substantial loss of seed mussels during the early stages of longline aquaculture—often exceeding 95%—is a major issue that erodes the security and profitability of production while limiting the sustainable expansion of this industry in many parts of the world. There are many biological, environmental and procedural factors that potentially cause seed losses. The present understanding of these factors is highly limited, based on disparate lines of evidence and constrained by the challenges associated with quantifying the fate of minute organisms in the field. Addressing these knowledge gaps is a prerequisite for meeting the growing global demand for farmed seafood and requires significant and coherent research. We identify the diverse range of potential drivers of seed loss in mussel aquaculture and review existing knowledge around these factors to identify critical knowledge gaps and research priorities. Losses appear to be caused by a complex suite of interacting factors that include stress during transfer between regions, underlying variations in seed condition, change in the farm environment, predation, competition from biofouling organisms and migratory behaviour of seed mussels. Solutions to the losses of mussel seed in commercial culture are mostly likely to be achieved through research directed at evaluating a range of practical interventions during the critical phase of nursery culture of mussel seed.