This review deals with the most meaningful historical topics on the study of synovial fluid, by starting from the Greco-Roman Medicine, up to Paracelsus (1493-1541), who introduced the term "synovia" to name the intra-articular humour. Afterwards, some till now unreported historical sources are recorded, e.g., a short text by the Italian XVIII century physician Giambattista Contoli ("Breve Instruzione sopre il Glutine, ò Colla., 1699"). Then, in keeping with some recent researches, a brief history of arthrocentesis is outlined, by considering the first procedures, which should have been performed in Mexico, during the precolonial period. Moreover, the first chemical analysis of synovial fluid, as carried out by the French chemist Jean-Louis Margueron (1792), and the first modern study on the synovial membrane by Marie-François-Xavier Bichat (1800) are explained. Finally, some XIX century investigations concerning the synovial pharmacodynamics, in particular an Italian one based on the elimination of certain chemical substances through the synovial membrane, are discussed.