Malignant pleural effusion (MPE) is a common complication of advanced malignancies, particularly lung and breast cancer. The survival time of patients with MPE is often short, with poor quality of life. The pleural space normally contains a thin film of fluid that is regulated by the balance between production from systemic blood vessel filtration and lymphatic absorption. Tumourinduced disturbances of the pleural fluid production and clearance processes result in the development of MPE. Until recently the specific mechanisms underlying pleural fluid accumulation were poorly defined because studies of MPE pathogenesis were limited by a lack of animal models that could reproduce the pathobiology of human MPE. During the past decade, various research groups have established experimental models that mimic human pleural malignancies, including mice models that require either immunocompromised or immunocompetent mice for propagation of human or murine cancer induced-MPE, respectively. The experimental modelling of MPE has provided new insight into the biological behaviour of tumour cells and tumour-host interactions in the pleural cavity, paving the way for improved management of this end-stage condition.