Pharmaceuticals and their by-products are recalcitrant contaminants in water. Moreover, the high consumption of these drugs has many detrimental effects on body waters and ecosystems. In this timely review, the advances in molecular engineering of layered double hydroxides (LDH) that have been used for the removal of pharmaceutical pollutants are discussed. The approach starts from the strategies to obtain homogeneous synthesis of LDH that allow the doping and/or surface functionalization of different metals and oxides, producing heterojunction systems as well as composites with carbon and silica-based materials with high surface area. Adsorption is considered as a traditional removal of pharmaceutical pollutants, so the kinetic and mechanism of this phenomenon are analyzed based on pH, temperature, ionic strength, in order to obtain new insights for the formation of multifunctional LDH. Advanced oxidation methodologies, mainly heterogeneous photocatalysis and Fenton-like processes, stand out as the more efficient even to obtain the mineralization of the drugs. The LDH have the advantage of structural memory that favors regeneration processes. The reconstruction of calcined LDH can be used to improve drug removal, through a combination of adsorption capacity/catalytic activity. A meticulous analysis of the persistence, toxicity and bioaccumulation of the most common pharmaceuticals has allowed us to highlight the ability of the LDH to remove recalcitrant drugs at relatively low concentrations (ppm, ppb), in contrast to other mixed oxide nanostructures and homogeneous oxidation processes. In this sense, the mechanism of drug removal by LDH is discussed based on the importance of the use of composites, scavenger agents, Fenton and electro-Fenton processes, membranes, thin films and coatings, among others. In addition, the ecotoxicity of LDH is also reviewed to indicate that these layered structures can exhibit biocompatibility or high toxicity depending on the adsorbed drug and ions/metals that compose them. Undoubtedly, the LDH have a unique flexible structure with adsorption capacity and catalytic activity, facts that explain the important reasons for their extensive use in the environmental remediation of pharmaceutical pollutants from water. •LDH nanomaterials can resolve the actual emerging pharmaceutical pollutants issues.•The use of LDH positively affects the water cycle to overcome toxic waste.•LDH can work as an adsorbent/catalytic agent for removal of pharmaceuticals.•Reconstruction of calcined LDH can be used to improve drug removal.