Distinct subpopulations of macrophages can be defined by their tissue of residence and functional phenotype. Select mouse tissue-resident macrophage populations that have been identified include adipose tissue-associated macrophages, osteoclasts and bone marrow macrophages in the bone, microglia, perivascular and meningeal macrophages in the central nervous system, intestinal lamina propria macrophages in the gastrointestinal tract, Kupffer cells in the liver, alveolar macrophages in the lung, large and small peritoneal macrophages in the peritoneal cavity, pleural macrophages in the pleural cavity, Langerhans cells and dermal macrophages in the skin, and splenic red pulp macrophages, marginal zone macrophages, marginal metallophilic macrophages, and white pulp macrophages. Each of these macrophage populations can be identified based on their expression or lack of expression of specific cell surface receptors and intracellular markers. Due to local stimuli in their environments or specialized functions associated with their tissue of residence, tissue-resident macrophages frequently express specific transcription factors that direct their activities. Macrophages also display great flexibility and plasticity depending on signals in their environments. As a result, their markers can be altered by external stimuli that modify their transcriptional programs and lead to an activated state.