Postsurgical intra-abdominal adhesions cause significant morbidity and mortality, with small bowel obstruction being the most common complication. The urge to prevent adhesion formation has resulted in multiple experimental and clinical trials and the development of numerous antiadhesive agents. Through the years, hyaluronan-based antiadhesives have proved to be successful in the reduction of adhesion formation. Despite the obvious effectiveness of hyaluronan, there is still much debate on its clinical use and mechanisms of action. Various hyaluronan-containing products have been introduced and withdrawn from the market. The application of hyaluronan in combination with meshes for hernia repair appears to be a promising concept. Not all different applications of hyaluronan are well known and its use in patients with a malignancy or abdominal infection remains controversial. Here an overview is given on the effects of hyaluronan-based antiadhesive agents in abdominal surgery, its use in infectious conditions, and its oncologic repercussions. The most important mechanism of action appears to be the mechanical separation of damaged peritoneal surfaces. However, the biological effects of hyaluronan, such as modulation of cell proliferation and peritoneal biology, might also be of influence.