In general, under isoweight conditions, different types of dietary protein or individual amino acids have little effect on lipoprotein patterns. Dietary carbohydrate tends to increase plasma triglyceride when it displaces fat, accompanied by a decrease in HDL cholesterol concentrations. Potential differential effects of types of carbohydrate are difficult to assess because of differences in rates of absorption and confounding of dietary fiber. Saturated fatty acids increase LDL and HDL cholesterol, whereas trans fatty acids increase LDL but not HDL cholesterol. Unsaturated fatty acids decrease LDL and HDL cholesterol, polyunsaturated more so than monounsaturated. There has been considerable interest in the potential benefit of major shifts in dietary macronutrients on weight loss and lipoprotein patterns. Short-term data favor substituting protein and fat for carbohydrate, whereas long-term data have failed to show a benefit for weight loss. During an active weight loss period low-carbohydrate diets more favorably affect triglyceride and HDL and less favorably affect LDL cholesterol concentrations. Additional efforts need to be focused on gaining a better understanding of the effect of dietary macronutrient profiles on established and emerging cardiovascular disease risk factors, mechanisms for changes observed and contributors to individual variability. Such data are needed to allow reassessment and, if necessary, modification of current recommendations. Dietary fat, carbohydrate, and protein are the primary energy-containing macronutrients consumed on a routine basis by humans. Dietary alcohol provides a unique category of energy and will not be considered in this review. Trendy weight loss diets that have flourished during the past decade have resulted in the generation of a considerable amount of data on how major shifts in the macronutrient content of the diet affect plasma lipoprotein patterns. These data can be used to inform dietary recommendations to minimize the risk of developing cardiovascular disease (CVD).It is difficult to consider the independent effect of dietary fat, carbohydrate, or protein on plasma lipoprotein patterns because, in each case, in addition to contributing unique essential and nonessential nutrients, the macronutrients also contribute the majority of metabolic energy to sustain life. To maintain a stable body weight, if the intake of one macronutrient is increased or decreased, there needs to be a compensatory adjustment in one or both of the other macronutrients. Under these circumstances, the effect observed on plasma lipoprotein patterns can be attributable to either the addition of one macronutrient or the reduction of the other(s). If a single macronutrient is increased or decreased without compensatory adjustments in the amount of the other macronutrients, body weight will change and any effect on plasma lipoprotein patterns will result from changes induced by weight loss or gain, a shift in the relative energy distribution of each macronutrient, or some combinati...