Forward genetics inDrosophilahas profoundly affected our understanding of circadian rhythms in this organism and, more generally, in the animal kingdom. MostDrosophilapacemaker genes were discovered through the isolation of gene variants affecting the free-running period of the circadian pacemaker. There are different ways to mutagenize flies. An alkylating agent can be used to randomly alter the fly genome, or transposable elements can be mobilized to disrupt or increase the expression of the targeted genes. The advantages of these different methods are complementary.