This review highlights the applications of the Keck allylation reaction in the synthesis of medicinally important natural products. Keck allylation is a versatile chemical reaction used for the conversion of a variety of aldehydes into homoallylic alcohols and has many applications in the synthesis of biologically active natural products. Efforts have been made to comprehensively provide an overview of the role of the Keck allylation reaction in the synthesis of natural products including the synthesis of macrolides, phorboxazole B, mandelalide A, rhizopodin, palmerolide A, belactosin A and hormaomycin, bryostatin I, the anti-tumor drug epothilones B, and the anti-obesity drug orlistat. This review will be beneficial for the biological and synthetic communities.