Multicomponent reactions (MCRs) offer a highly useful and valuable strategy that can fulfill an important role in synthesizing complex polysubstituted compounds, by simplifying otherwise long sequences and increasing their efficiency. The total synthesis of selected natural products employing three‐component reactions as their common strategic MCR approach, is reviewed on a case‐by‐case basis with selected targets conquered during the last 15 years. The revision includes detailed descriptions of the selected successful sequences; relevant information on the isolation, and bioactivity of the different natural targets is also briefly provided.