CVD remains the greatest cause of death globally, and with the escalating prevalence of metabolic diseases, including type-2 diabetes, CVD mortality is predicted to rise. While the replacement of SFA has been the cornerstone of effective dietary recommendations to decrease CVD risk since the 1980s, the validity of these recommendations have been recently challenged. A review of evidence for the impact of SFA reduction revealed no effect on CVD mortality, but a significant reduction in risk of CVD events (7–17%). The greatest effect was found when SFA were substituted with PUFA, resulting in 27% risk reduction in CVD events, with no effect of substitution with carbohydrate or protein. There was insufficient evidence from randomised controlled trials to conclude upon the impact of SFA replacement with MUFA on CVD and metabolic outcomes. However, there was high-quality evidence that reducing SFA lowered serum total, and specifically LDL-cholesterol, a key risk factor for CVD, with greatest benefits achieved by replacing SFA with unsaturated fats. The exchange of SFA with either PUFA or MUFA, also produced favourable effects on markers of glycaemia, reducing HbA1c, a long-term marker of glycaemic control. In conclusion, the totality of evidence supports lowering SFA intake and replacement with unsaturated fats to reduce the risk of CVD events, and to a lesser extent, cardiometabolic risk factors, which is consistent with current dietary guidelines.