The Robinson annulation is a significant reaction for the synthesis of α,β‐unsaturated ketone ring including the generation of two C−C bonds. It involves a Michael addition of a ketone and a methyl or ethyl vinyl ketone with subsequent intramolecular aldol condensation. Natural products and their structurally related analogues have historically made a major contribution to pharmacotherapy, particularly for cancer and infectious diseases. The Robinson annulation has frequently been employed as a vital step in the total synthesis of these important naturally occurring compounds and related complex biologically active products. In this review, we try to underscore the applications of the Robinson annulation in the total synthesis of biologically active natural products.