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The use of emerging multicomponent reactions (MCRs) in conjunction with microwave (MW)-assisted chemistry techniques is dramatically reducing chemical waste and reaction times in several organic syntheses and chemical transformations. MW-assisted active methylene-based multicomponent reactions serve as a rapid and efficient tool for the synthesis of versatile heterocycles, particularly those containing structural diversity and complexity via a one-pot operation. This minireview covers our recent advances on multicomponent reactions involving active methylene compounds for the construction of bioactive molecule skeletons. In many cases, MW-assisted MCRs offer considerable improvements in selectivity, chemical yield and purity and constitutes a very simple and extremely rapid method to access a diverse range of heterocyclic motifs.