Tetraspanins, also called tetraspans or the transmembrane 4 superfamily (TM4SF), are cell-surface proteins that span the membrane four times and are found on many different cell types in many organisms. They display numerous properties that indicate their physiological importance in cell adhesion, motility, activation and proliferation, as well as their contribution to pathological conditions such as metastasis or viral infection. A major characteristic of tetraspanins is their ability to form cell-surface complexes with other molecules participating in cell adhesion, either to the extracellular matrix (ECM) or to other cells, and with molecules required for signalling. It is not yet known how the structure of the complexes might affect the functions of other molecules or what basic biochemical mechanisms allow their formation and regulation. Nevertheless, an intriguing association between tetraspanin expression and metastatic potential indicates that these molecules may provide novel insights into tumour progression.