Clinical practice guidelines are an essential mechanism for translating evidence into practice and supporting healthcare professionals to provide evidence-based clinical care. Few such guidelines incorporate recommendations for deprescribing—the supervised process of reducing or stopping medications where the harms outweigh the benefits. This omission has been highlighted by healthcare professionals as a significant barrier to making deprescribing decisions. To address this gap, drug class-specific evidence-based deprescribing guidelines have been developed over the last decade for proton pump inhibitors, benzodiazepine receptor agonists, antipsychotics, antihyperglycemics, cholinesterase inhibitors and memantine, and opioids. Increasing the availability of evidence-based deprescribing guidance can also be supported by integrating deprescribing recommendations into all clinical practice treatment guidelines that include pharmacotherapy recommendations. In general, despite a growing number of clinical practice guidelines related to screening, diagnosis, treatment, and public health, their use in practice is highly variable with guideline nonadherence rates exceeding 50%. With this knowledge, there are a growing number of tools to support implementation of deprescribing guidelines including healthcare provider and consumer-directed resources, videos, mobile apps, and other communication tools. More research is needed to measure and learn how to best implement deprescribing recommendations and guidelines into practice.