In the past decade, alternative benign organic methodologies have become an imperative part of organic syntheses and chemical reactions. The various new and innovative sustainable organic reactions and methodologies using no solvents or catalysts and employing alternative energy inputs such as microwaves, sonication, conventional and room temperature heating conditions, mechanochemical mixing, and high-speed ball milling are discussed in detail. Environmentally benign and pharmaceutically important reactions such as multicomponent, condensation, and Michael addition reactions; ring opening of epoxides; and oxidation and other significant organic reactions are discussed. An overview of benign reactions through solvent- and catalyst-free (SF-CF) chemistry and a critical perspective on emerging synergies between SF-CF organic reactions are discussed.