Judgments as to causality of associations between risk factors and disease involve a weighing of the available evidence from animal and human studies. The human data include observational studies, results of which may be confounded, and randomized trials, which may be unavailable or infeasible, thus limiting the ability to make causal inference. Mendelian randomization offers an additional approach to help assess causality. The concept relies on the random assignment of alleles at meiosis as the basis for a natural randomized experiment linking genetic variants to intermediate risk factors and disease. Recent Mendelian randomization studies have provided evidence for a causal role of serum lipoprotein(a) in coronary heart disease, and against a causal role for plasma C-reactive protein. Although a valid Mendelian randomization experiment is subject to a number of assumptions and limitations, it is a useful adjunct to assess causality, especially when randomized trials are unavailable.