The present application relates to monoclonal antibodies and antigen-binding portions thereof, that specifically bind to the C-terminal or the center region of macrophage migration inhibitory factor (MIF). These anti-MIF antibodies and antigen-binding portions thereof further inhibit human MIF biological function. The application also relates to isolated heavy and light chain immunoglobulins derived from the anti-MIF antibodies and nucleic acid molecules encoding such immunoglobulins. The present application also relates to a method of identifying anti-MIF antibodies, pharmaceutical compositions comprising these antibodies and a method of using these antibodies and compositions for the treatment of MIF-related conditions.