As melanoma is an immunogenic tumor, immunotherapy has been investigated as a possible treatment modality for melanoma patients at high risk of relapse and those with metastatic disease. In the past decade progress has been made, ranging from rather nonspecific stimulations of the immune system with IL-2 and IFN-alpha to more specific approaches based on vaccination with tumor antigens. Owing to their unique features, dendritic cells (DCs) represent an important tool for tumor antigen-specific immunotherapy. However, clinical vaccination trials with DCs showed sobering results with respect to objective responses and improvement of overall survival. In this review, principles and methods of DC-based vaccination are presented. Mechanisms impairing clinically successful vaccination strategies are described. Finally, we will discuss perspectives for future developments of DC-based vaccines that might lead melanoma treatment to a new era.