Five patients are reported who have pleural effusion and pyogenic vertebral osteomyelitis. In four of the five patients, the presenting problem was a large pleural effusion, and three of these four patients had an exudative effusion. Initial evaluation and investigations in these patients were directed toward the pleuropulmonary disease, delaying the diagnosis of osteomyelitis, and in two patients, this delay resulted in neurologic complications. In the fifth patient, the pleural effusion was initially small; however, during the course of a workup for osteomyelitis, the effusion increased rapidly. Two out of the five patients had empyema, and the other three patients had a large pleural effusion associated with and apparently caused by vertebral osteomyelitis. Vertebral osteomyelitis should be considered in the differential diagnosis of pleural effusion of uncertain cause especially if there is associated back pain.