|Dietary guidelines in many countries include a recommendation to consume oily fish, mainly on the basis of evidence from prospective cohort studies that fish consumption is cardioprotective. However, average intakes are very low in a large proportion of the UK population. Some groups, such as vegans and vegetarians, purposely omit fish (along with meat) from their diet resulting in zero or trace intakes of long chain (LC) n-3 PUFA. Although the efficacy of dietary fish oil supplementation in the prevention of CVD has been questioned in recent years, the balance of evidence indicates that LC n-3 PUFA exert systemic pleiotropic effects through their influence on gene expression, cell signalling, membrane fluidity and by conversion to specialised proresolving mediators; autacoid lipid mediators that resolve inflammatory events. The long-term impact of reduced tissue LC n-3 PUFA content on cardiovascular health is surprisingly poorly understood, particularly with regard to how low proportions of LC n-3 PUFA in cell membranes may affect cardiac electrophysiology and chronic inflammation. Randomised controlled trials investigating effects of supplementation on prevention of CHD in populations with low basal LC n-3 PUFA tissue status are lacking, and so the clinical benefits of supplementing non-fish-eating groups with vegetarian sources of LC n-3 PUFA remain to be determined. Refocusing dietary LC n-3 PUFA intervention studies towards those individuals with a low LC n-3 PUFA tissue status may go some way towards reconciling results from randomised controlled trials with the epidemiological evidence.