The hyaluronan (HA) polymer is a critical component of extracellular matrix with a remarkable structure: is a linear and unbranched polymer without sulphate or phosphate groups. It is ubiquitous in mammals showing several biological functions, ranging from cell proliferation and migration to angiogenesis and inflammation. For its critical biological functions the amount of HA in tissues is carefully controlled by different mechanisms including covalent modification of the synthetic enzymes and epigenetic control of their gene expression. The concentration of HA is also critical in several pathologies including cancer, diabetes and inflammation. Beside these biological roles, the structural properties of HA allow it to take advantage of its capacity to form gels even at concentration of 1 % producing scaffolds with very promising applications in regenerative medicine as biocompatible material for advanced therapeutic uses. In this review we highlight the biological aspects of HA addressing the mechanisms controlling the HA content in tissues as well as its role in important human pathologies. In the second part of the review we highlight the different use of HA polymers in the modern biotechnology.