<p>Macrophages regulate inflammatory and fibrotic processes in several autoimmune and inflammatory rheumatic diseases. They are highly plastic cells, shifting within a range of pro-inflammatory and anti-inflammatory or pro-fibrotic phenotypes in response to dynamic interactions with other cells, environmental factors and cytokine signatures. The terms ‘M1 macrophages’, or classically activated, and ‘M2 macrophages’, or alternatively activated, were previously used to denote pro- and anti-inflammatory macrophage subsets, respectively, but this classification system has been outdated by in vivo evidence of a continuum of macrophage phenotypes that includes M1-like, M2-like and hybrid phenotypes. Deciphering the specific mechanisms that drive macrophage plasticity and function during the progression of rheumatoid arthritis, psoriatic arthritis, systemic sclerosis, systemic lupus erythematosus, and in synovitis and large vessel vasculitis in polymyalgia rheumatica and giant-cell arteritis, can improve our understanding of disease pathophysiology. Macrophage plasticity is enhanced in synovial tissue in rheumatoid arthritis, fibrotic skin and lung in systemic sclerosis, damaged kidney in systemic lupus erythematosus, and the bursal tissues or large vessels in polymyalgia rheumatica and giant-cell arteritis. Sophisticated transcriptomic analyses have revealed various phenotypic clusters of macrophages in biopsies of affected organs. Moreover, macrophage plasticity seems to be targeted by some standardized drugs used to treat the aforementioned conditions.</p>