Over the past decade, the advent of targeted therapy (TT; BRAF and MEK inhibitors), immune checkpoint inhibitors (ICIs), and inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1) alone or combined with cytotoxic T-lymphocyte-associated antigen-4 inhibitors (CTLA-4) has considerably improved the survival of patients with unresectable stage III-IV melanoma. This evidence concerns the gene PDCD1 and melanoma.