Macrophages are versatile cells involved in health and disease. These cells act as scavengers to rid the body of apoptotic and senescent cells and debris through their phagocytic function. Although this is a primary function of these cells, macrophages play vital roles in inflammation and repair of damaged tissue. Macrophages secrete a large number of cytokines, chemokines and growth factors that recruit and activate a variety of cell types to inflamed tissue compartments. These cells are also critical in cell-mediated immunity and in the resolution of inflammation. Since macrophages, and their precursors, blood monocytes, are important in regulating and resolving inflammation, prolonged cellular survival in tissue compartments could be detrimental. Thus, factors that regulate the fate of monocyte and macrophage survival are important in cellular homeostasis. In this article, we will explore stimuli and the intracellular pathways important in regulating macrophage survival and implication in human disease.