Macrophages are divided into several functional subtypes involved in host defence, wound healing and immune regulation. In an alternate view, increased understanding of macrophage biology can also be gained by including anatomical location as a parameter. The focus of this review lies on tolerogenic features of macrophages relevant for autoimmune disease. The importance of macrophages as janitors clearing apoptotic cells and debris is seen in systemic lupus erythematosus (SLE) where a clearance defect often is connected to disease induction and progression. The apoptotic debris can be encountered by the macrophage in multiple anatomical compartments including the circulation but also in areas of intense cell death such as in the thymus and germinal center were tight regulation is important.