The aim of aetiologic studies in epidemiology is to investigate whether factors are causally related to diseases and therefore become a potential target for therapeutic interventions. Mendelian randomization enables estimation of causal relationships in observational studies using genetic variants as instrumental variables. An instrumental variable is a variable that can be considered to mimic the coin toss in a randomized study. Given the random assignment of alleles in gamete formation, the use of genetic variants is an alternative method to control for confounding. This educational article describes the approach of Mendelian randomization, its underlying rationale and its necessary assumptions.