Proton pump inhibitors (PPIs) are among the most widely used class of drugs prescribed over the long term in all of clinical medicine with 8–10% of ambulatory adults have been prescribed a PPI in the past 30 days. However, numerous studies have raised doubts about the long term safety of PPI use. The purpose of this review is threefold: (i) To provide an overview of the current evidence demonstrating associations between PPI use and adverse health outcomes and the likelihood of the associations being causal (Why?); (ii) To be able to identify long-term PPI users in whom the intensity of PPI therapy could be reduced or in whom PPIs could be eliminated outright (Who?); and (iii) To provide strategies on how to reduce or stop chronic PPI therapy while maintaining symptom control and reducing the risk for symptom or upper GI disease recurrence (How?).

质子泵抑制剂（PPI）是所有临床药物中长期使用的最广泛使用的药物之一，在过去30天内，有8–10％的非卧床成年人已使用PPI。但是，许多研究对PPI的长期安全性提出了疑问。审查的目的是三方面的：（i）提供当前证据的概述，这些证据表明PPI的使用与不良健康后果之间的关联以及这种关联具有因果关系的可能性（为什么？）；（ii）能够确定可以降低PPI治疗强度或可以完全消除PPI的长期PPI用户（谁？）；（iii）提供有关如何在维持症状控制并降低症状或上消化道疾病复发风险的同时减少或停止慢性PPI治疗的策略（如何？）。