A large number of drugs are known to cause lung injury, and their number is increasing, mainly due to the development of drugs with specific mechanistic targets such as immune checkpoint inhibitors (and other antineoplastic agents), monoclonal antibodies and tyrosine kinase inhibitors. Drug-induced lung injury (DILI) is difficult to diagnose since it has no distinctive features and almost always presents against a background of confounding issues. Therefore, most usually, DILI is a diagnosis of exclusion. This chapter explores the issues that potentially confound the approach to a possible case of DILI and the questions to raise while approaching a potential case of DILI. It presents the information that is required for a provisional diagnosis of DILI and demonstrates how it is possible to construct a symptom-based approach to the condition. It also shows how the diagnosis can be narrowed down based on HRCT and histopathological patterns. It also discusses the mechanisms of DILI that provide the background information that is necessary to evolve a diagnostic approach.