An imbalance of dietary lipids may potentially have a significant role in the pathobiology of some chronic diseases. Public health dietary fat recommendations have emphasized that low saturated fat, high monounsaturated fat, and high polyunsaturated fat with a lower ω-6 to ω-3 fatty acid ratio intake are necessary for normal health. However, such universal recommendations are likely to be hazardous, since the outcome of recommended lipid intake may depend on the consumption of other important dietary constituents that have an important role in the metabolism of lipids. In addition, consumption of fatty acids as per the individually tailored specific requirements in the context of other nutritional factors may have the potential to stabilize hormones, mood and sleep, and minimize adverse events. In support of this proposal, we review various factors that influence fatty acid metabolism, which need to be taken into consideration for appropriate utilization and consequently prevention of various diseases.