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ABSTRACT Introduction Pleural diseases encompass a broad range of conditions with diverse and heterogenous etiologies. Diagnostics in pleural diseases thus represents a challenging field with a wide array of available testing to distinguish between the numerous causes of pleural disease. Nonetheless, deploying best practice diagnostics in this area is essential in reducing both duration o the investigation pathway and symptom burden. Areas covered This article critically appraises the optimal diagnostic strategies and pathway in patients with pleural disease, reviewing the latest evidence and key practice points in achieving a treatable diagnosis in patients with pleural disease. We also cover future and novel directions that are likely to influence pleural diagnostics in the near future. PubMed was searched for articles related to pleural diagnostics (search terms below), with the date ranges including June 2012 to June 2022. Expert opinion No single test will ever be sufficient to provide a diagnosis in pleural conditions. The key to reducing procedure burden and duration to diagnosis lies in personalizing the investigation pathway to patients and deploying tests with the highest diagnostic yield early (such as pleural biopsy in infection and malignancy). Novel biomarkers may also allow earlier diagnostic precision in the near future.