Adiponectin is the most abundant adipokine circulating in the organism. Different molecular forms of adiponectin exist: low, middle and high molecular isoforms, as well as globular adiponectin, all of which have different biological properties. Adiponectin is considered a key adipokine in metabolic diseases such as type 2 diabetes, metabolic syndrome and related complications, especially cardiovascular diseases. In these metabolic conditions, circulating adiponectin is reduced. It is now well known that adiponectin has beneficial effects on endothelial cells and endothelial function and is also cardioprotective. Unlike metabolic diseases, systemic autoimmune and chronic inflammatory joint diseases are characterized by increased production of adiponectin. There is evidence to suggest that adiponectin may be related to disease activity and/or severity in different conditions such as rheumatoid arthritis, systemic lupus erythematosus and osteoarthritis. Since adiponectin has been found to display both pro and anti-inflammatory activities, controversial findings have been observed on the role of total adiponectin in systemic autoimmune and inflammatory joint diseases. Thus, the relative contribution of each adiponectin isoform to the inflammatory response and joint and/or tissue damage requires further study.