Epistasis, i.e., the fact that gene effects depend on the genetic background, is a direct consequence of the complexity of genetic architectures. Despite this, most of the models used in evolutionary and quantitative genetics pay scant attention to genetic interactions. For instance, the traditional decomposition of genetic effects models epistasis as noise around the evolutionarily-relevant additive effects. Such an approach is only valid if it is assumed that there is no general pattern among interactions—a highly speculative scenario. Systematic interactions generate directional epistasis, which has major evolutionary consequences. In spite of its importance, directional epistasis is rarely measured or reported by quantitative geneticists, not only because its relevance is generally ignored, but also due to the lack of simple, operational, and accessible methods for its estimation. This paper describes conceptual and statistical tools that can be used to estimate directional epistasis from various kinds of data, including QTL mapping results, phenotype measurements in mutants, and artificial selection responses. As an illustration, I measured directional epistasis from a real-life example. I then discuss the interpretation of the estimates, showing how they can be used to draw meaningful biological inferences.