Although inflammation has a physiological role, unrestrained inflammation can be detrimental, causing tissue damage and disease. Under normal circumstances inflammation is self-limiting with induction of active resolution processes. Central to these is the generation of specialised pro-resolving lipid mediators (SPMs) from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These include resolvins, protectins and maresins whose activities have been well described in cell and animal models. A number of SPMs have been reported in plasma or serum in infants, children, healthy adults and individuals with various diseases, as well as in human sputum, saliva, tears, breast milk, urine, synovial fluid and cerebrospinal fluid and in human adipose tissue, skeletal muscle, hippocampus, skin, placenta, lymphoid tissues and atherosclerotic plaques. Differences in SPM concentrations have been reported between health and disease, as would be expected. However, sometimes SPM concentrations are lower in disease and sometimes they are higher. Human studies report that plasma or serum concentrations of some SPMs can be increased by increasing intake of EPA and DHA. However, the relationship of specific intakes of EPA and DHA to enhancement in the appearance of specific SPMs is not clear and needs a more thorough investigation. This is important because of the potential for EPA and DHA to be used more effectively in prevention and treatment of inflammatory conditions. If generation of SPMs represents an important mechanism of action of EPA and DHA, then more needs to be known about the most effective strategies by which EPA and DHA can increase SPM concentrations.