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Cardioprotective effects of OO consumption have been widely related with improved lipoprotein profile, endothelial function and inflammation, linked to health claims of oleic acid and phenolic content of OO. With CVD being a leading cause of death worldwide, a review of the potential mechanisms underpinning the impact of OO in the prevention of disease is warranted. The current body of evidence relies on mechanistic studies involving animal and cell-based models, epidemiological studies of OO intake and risk factor, small- and large-scale human interventions, and the emerging use of novel biomarker techniques associated with disease risk. Although model systems are important for mechanistic research nutrition, methodologies and experimental designs with strong translational value are still lacking. The present review critically appraises the available evidence to date, with particular focus on emerging novel biomarkers for disease risk assessment. 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