Obesity represents a rising global health concern, linked to significant social, psychological and physical burden to the individual affected, people around them and the society as a whole. Obesity has been described as a low-grade inflammatory condition, associated with increased production of pro-inflammatory mediators like tumor necrosis factor alpha or interleukin 6 and altered expression of adipokines. Adipokines, mainly produced by adipose tissue, have mixed pro- and anti-inflammatory properties. Obesity rarely exists on its own; instead, it tends to coexist with (often multiple) other comorbidities, including metabolic, cardiovascular, and rheumatic and musculoskeletal diseases (RMDs). In the case of RMDs, evidence is rapidly accumulating on common mechanistic pathways implicated in the inflammatory states seen between RMDs and obesity. Although there remain unanswered questions on the exact mechanisms of inflammation that link obesity to RMDs, what is becoming increasingly known is the association between obesity and adverse clinical outcomes in RMDs. This narrative review discusses insights into mechanisms of inflammation linking obesity and RMDs and evidence on the impact of obesity on treatment response and important disease outcomes. We highlight the importance of targeting obesity, a common and modifiable comorbidity, as part of the routine care of people with RMDs.