The objectives of this article are to review clinical trials that have examined the effects of probiotics on low-density lipoprotein cholesterol (LDL-C) and to assess the potential of probiotic intake as a therapeutic lifestyle change (TLC) dietary option. Twenty-six clinical studies and two meta-analyses are reviewed. Significant LDL-C reductions were observed for four probiotic strains: Lactobacillus reuteri NCIMB 30242, Enterococcus faecium, and the combination of Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12. Two synbiotics, L. acidophilus CHO-220 plus inulin and L. acidophilus plus fructo-oligosaccharides, also decreased LDL-C. Of the probiotics examined, L. reuteri NCIMB 30242 was found to best meet TLC dietary requirements by 1) significantly reducing LDL-C and total cholesterol, with robustness similar to that of existing TLC dietary options, 2) improving other coronary heart disease risk factors, such as inflammatory biomarkers, and 3) having “generally recognized as safe” (GRAS) status. Based on these results, the probiotic L. reuteri NCIMB 30242 is a viable candidate both for future TLC dietary studies and as a potential option for inclusion in TLC dietary recommendations.