Sarcoidosis is a multisystem disorder of unknown cause(s). Despite the knowledge gained during the last decade regarding the pathogenetic mechanisms accounting for the onset, maintenance or evolution of the disease, its etiology is still elusive. To solve this problem, the National Heart, Lung, and Blood Institute (NHLBI) set up a multicenter study, i.e. the ACCESS study (A Case Control Etiologic Study of Sarcoidosis). The study has been designed to validate four major categories of etiological hypotheses (genetic, environmental, infectious and immune dysregulation hypotheses) and its primary endpoint is the discovery of the cause(s) of sarcoidosis. A definite etiology of sarcoidosis was not found, however, the results of ACCESS offer hypotheses for future targeted studies in the search for the cause(s) of the disease and a rich base of case and control data was established for future studies. Lessons learned from ACCESS suggest that hope for finding the etiology of sarcoidosis comes from large, collaborative studies.