In this review, we summarize the data about applications of squaric acid, its derivatives and their metal complexes in medicine. In recent years, researchers have been concentrated on the study of squaric acid and its derivatives because of their unique properties and the different possible ways to coordinate with metals and form complex compounds. Encouraging results have also been obtained for the cytotoxic activity of some squaric acid analogues and their metal complexes on various human tumor cell lines.