Although the initiating factor(s) is unknown, it is now accepted that pulmonary sarcoidosis develops as a result of an over-stimulated local cellular immune response. Starting as a lymphocytic alveolitis, there is a progression to granuloma formation within the interstitium as stimulated T lymphocytes release mediators capable of attracting and activating monocytes to differentiate into macrophages and epithelioid cells. We are also aware that macrophage-like cells must act as antigen presenters to initiate T cell stimulation within the immune response. To date, interest in the alveolar macrophages of patients with sarcoidosis has focused more on their passive role as responders of the soluble T cell products released as the disease progresses. This paper explores the active role of mononuclear non-lymphoid cells as inducers of immune responses, by taking advantage of monoclonal antibodies capable of discriminating between phenotypically distinct subsets of macrophages. Recent results are presented that suggest a central role for these cells in controlling the course of this disease, focusing specifically on the mechanisms underlying the failure in some patients to resolve the interstitial inflammation and subsequently progressing to fibrosis. A new hypothesis proposes that aberrations in the functional capacity of macrophages may prohibit the emergence of a granuloma-resolving mechanism in some sarcoid patients.