The Diels–Alder reaction, first described in 1928, is one of the most celebrated and versatile transformations in organic chemistry. This reaction enables the efficient construction of six-membered rings with remarkable regio- and stereocontrol, making it indispensable for synthesizing complex natural products and pharmaceuticals. Over the decades, methodological advancements such as asymmetric catalysis, organocatalysis, and inverse electron demand variants have expanded its scope, allowing the synthesis of highly functionalized and stereochemically dense frameworks. Biomimetic applications have further bridged the gap between chemical synthesis and natural product biogenesis, while the discovery of Diels–Alderases has unveiled the ability of Nature to catalyze pericyclic reactions with exceptional efficiency and stereocontrol. The reaction has been pivotal in addressing synthesis challenges posed by intricate natural products, such as vinigrol, scabrolide, and the manzamine alkaloids, and continues to evolve with emerging applications in sustainable chemistry, photochemical activation, and enzyme engineering. This volume highlights the historical significance, methodological innovations, biomimetic strategies, enzymatic catalysis, and future directions of the Diels–Alder reaction, underscoring its enduring relevance as a cornerstone of chemical innovation.