Background <p>Pleural effusion represents a&#xa0;pathological accumulation of fluid within the pleural cavity and it is not a&#xa0;disease entity in itself but the consequence of various pleural, pulmonary or systemic disorders. In Germany an estimated 400,000–500,000 cases occur annually. Due to this high prevalence and wide range of underlying causes pleural effusion is a&#xa0;frequent reason for further diagnostic evaluation and sometimes has significant prognostic relevance.</p> Objective <p>The aim of this article is to provide a&#xa0;structured, guideline-based and practical overview of the diagnostic approach to pleural effusion. Clinical, imaging, laboratory, microbiological, cytological and invasive procedures are assessed with respect to the diagnostic value and indications.</p> Material and methods <p>This article is based on a&#xa0;comprehensive review of current guidelines and studies. It outlines a&#xa0;stepwise diagnostic approach including medical history, physical examination, imaging (chest X‑ray, thoracic ultrasound, computed tomography), thoracentesis and pleural fluid analysis. The indications and the diagnostic yield of thoracoscopy are also discussed.</p> Results <p>The structured diagnostic approach enables a clear identification of the underlying etiology in most cases. Thoracic ultrasound demonstrates a higher sensitivity than chest radiography for detecting small effusions and is considered the gold standard for diagnostics and procedural guidance. The utilization of Light’s criteria enables the biochemical differentiation between transudates and exudates with a&#xa0;sensitivity of over 95%. The microbiological analysis of pleural fluid using blood culture bottles and PCR assays significantly increases the detection rate of infectious causes. In suspected malignant effusions cytology shows a mean sensitivity of approximately 58%, therefore thoracoscopy with a targeted biopsy should be performed in cases with a negative cytology result.</p>