A growing body of research offers insight into the influence of dietary protein on cardiovascular disease (CVD) risk. Early studies in rabbits indicated that animal protein was atherogenic; however, this has not been demonstrated in other animals species (pig, primate) or humans. More recent studies have found that low-fat animal protein can effectively improve some CVD risk factors. Soy protein has received much attention in recent years due to its seemingly marked effect on plasma cholesterol levels. However, further research has shown the hypocholesterolemic effect of soy protein to be most pronounced in cases of moderate to severe elevations in plasma lipids. Still, animal and soy protein sources contain a variety of bioactive components that may offer protection above and beyond cholesterol reduction. This review provides evidence that as part of a low-saturated fat diet, animal and/or soy protein intake at or above the recommended intake level of 15% of total calories lowers plasma cholesterol levels, reduces blood pressure, and potentially facilitates healthy weight management.