The deactivation of catalysts and their regeneration are two very important challenges that need to be addressed for many industrial processes. The most quoted reasons for the deterioration of dimethyl ether synthesis (DME) concern the sintering and the hydrothermal leaching of copper particles, their migration to acid sites, the partial formation of copper and zinc hydroxycarbonates, the formation of carbon deposits, and surface contamination with undesirable compounds present in syngas. This review summarises recent findings in the field of DME catalyst deactivation and regeneration. The most-used catalysts, their modifications, along with a comparison of the basic parameters, deactivation approaches, and regeneration methods are presented.