Zamboni hypothesized that venous stasis resulting from cerebrospinal venous insufficiency (CCSVI) leads to increased iron deposition in the brain parenchyma, and that this iron triggers multiple sclerosis (MS) inflammatory activity. A number of authors have challenged the CCSVI hypothesis on several grounds including the redundancy of the venous system. CCSVI has received considerable attention from the mainstream media and the lay public. This has led to increasing pressure on physicians by patients seeking venous imaging and endovascular angioplasty, commonly referred to as the liberation procedure. New therapeutic strategies aimed at reducing venous pressures and venous reflux could be developed and might be more effective than the immunomodulatory and immunosuppressive therapies currently being used. It is, therefore, imperative to confirm and further characterize the association of CCSVI and MS before proceeding with interventional studies and, more importantly, venous procedures in clinical practice.