The Seven Countries Study suggested an association between serum cholesterol and cardiovascular disease (CVD). However, the association was not consistent across the various cohorts of participants in different countries; while it was very clear in US and Northern European cohorts, it was weak in Southern European and Japanese cohorts. Nevertheless, the study triggered research into cholesterol-lowering drug strategies, ultimately leading to the development of statins amongst others. Clinical evidence in support of statins is strong and the vast majority of the medical community advocate these drugs as highly effective first-line therapeutics in primary and secondary prevention of CVD. However, growing evidence of side-effects associated with statins in a significant proportion of patients suggests that these drugs are not a universal solution to CVD. There is a need, therefore, to revisit the evidence and to reappraise the relative importance of cholesterol amongst many other lipids as potential modulators of atherogenesis. In this review, we assess the relative merits of statin therapy in CVD versus dietary interventions that impact on lipids other than cholesterol, including omega-3 fatty acids and polar lipid fractions of various foods (e.g. fish and olive oil). We conclude that careful design around the lipid components of dietary interventions presents a credible alternative in patients who are intolerant to statins or averse to taking such drugs.