Malignant melanoma is the leading cause of death from diseases of the skin. This review summarizes the data from the literature and our laboratory addressing the effects of type IV collagen on melanoma progression. Many different sequences from type IV collagen promote melanoma cell adhesion, migration and invasion. The triple helical conformation of the collagenous domain plays a critical role in some of these interactions. However, recent studies from our group demonstrated that a sequence from the alpha3(IV) NC1 domain inhibits melanoma cell proliferation, migration and invasion by decreasing MMP production and activation. Peptide sequences from the alpha1(IV), alpha2(IV) and alpha3(IV) chains named arresten, canstatin and tumstatin, respectively were shown to inhibit angiogenesis. Further investigations regarding the inhibitory effects of the alpha(IV) NC1 domains will have a paramount relevance for the design of efficient strategies to limit melanoma development.