Melanoma have been shown to escape immune surveillance by different mechanisms such as loss of HLA class I antigens, upregulation of nonclassical HLA-G antigen and Fas, increased secretion of immune suppressive cytokines and metabolites as well as altered expression of co-stimulatory and coinhibitory signals. Recently, an important role of B7-H1 and B7-H4 in the immune escape of melanoma has been described. High mRNA and/or protein expression levels of these coinhibitory molecules were detected in both melanoma cell lines and melanoma lesions when compared to melanocytes. However, their clinical relevance is currently controversially discussed regarding a correlation of B7-H family members with tumor grading and staging as well as survival of patients in melanoma.