Transforming growth factor-β (TGF-β) plays a complex role during carcinogenesis. It may either act as a tumor suppressor through its broad antiproliferative potential or as a tumor promoter either via direct effects on tumor cell aggressiveness or indirectly by modulating stromal responses, angiogenesis and immune surveillance. Increased production of TGF-β by cancer cells is often associated with tumor grade. Melanoma cells largely escape cell cycle arrest normally induced by TGF-β in normal melanocytes, yet produce active TGF-β and are capable of efficient transcriptional responses to the growth factor. In this review, we summarize the current knowledge about the role played by TGF-β in melanoma progression and hypothesize about the appropriateness of targeting TGF-β signaling for therapeutic intervention.