Inflammation is the non-specific stereotyped reaction of the musculoskeletal system to various types of aggression, such as infection, tumor, autoimmune diseases, or trauma. Precise evaluation and, increasingly, reliable quantification of inflammation are now key factors for optimal patient management, as targeted therapies (e.g., anti-angiogenesis, anti-macrophages, anti-cytokines) are emerging as everyday drugs. In current practice, inflammation is evaluated mostly using MRI and US on the basis of its non-specific extracellular component due to the increased volume of free water. Inflamed tissue is described as areas of low T1 signal and high T2 signal on magnetic resonance imaging or as hypoechogenic areas on ultrasound imaging, and the evaluation of the increased tissue vascularity can be performed using gadolinium-enhanced MRI or power Doppler US. Emerging new imaging tools, regrouped under the label "cellular and molecular imaging" and defined as the in vivo characterization and measurement of biologic processes at the cellular and molecular level, demonstrate the possible shift of medical imaging from a macroscopic and non-specific level to a microscopic and targeted scale. Cellular and molecular imaging now allows the investigation of specific pathways involved in inflammation (e.g., angiogenesis, cell proliferation, and recruitment, proteases generation, metabolism, gene expression). PET and SPECT imaging are the most commonly used "molecular" imaging modalities, but recent progress in MR, US, and optical imaging has been made. In the future, those techniques might enable a detection of inflammation at its very early stage, its quantification through the definition of biomarkers, and possibly demonstrate the response to therapy at molecular and cellular levels.