Tumour cell adhesion, motility, proteolytic activities and cell receptors have important roles in cancer invasion. These processes are involved from early development of melanoma within the epidermis, to tumour cell invasion of the underlying tissue until intravasation of lymphatic or blood vessels, and thereafter, dissemination into distant organs occur. The activity of several proteolytic enzymes was shown to be pivotal in promoting melanoma cell invasion. These enzymes not only remodel the extracellular matrix, but also release active factors and shed cell surface receptors thereby mediating melanoma cross-communication with their microenvironment. This leads to the generation of a favourable environment for melanoma growth. Several proteases are involved in melanoma invasion and include serine, cysteine proteases, matrix metalloproteases (MMPs) and the disintegrin and metalloproteases (ADAMs). This study summarises the current knowledge on the role of metalloproteinases, MMPs and ADAMs, in melanoma.