Immunotherapy for the treatment of advanced melanoma has become a primary treatment in the clinic. Current therapies include systemic cytokines, immune checkpoint inhibitors, and localized intratumoral therapies. Checkpoint inhibitors block natural pathways that dampen or inhibit an immune response to stimulus. These pathways include programmed cell death 1 receptor/programmed death-ligand 1 and cytotoxic T lymphocyte antigen-4. Systemic immunotherapies have proven to be effective in clinical trials both as monotherapy and in combination therapy. Oncolytic viruses are used to treat tumor locally and induce an effective immune response. Although some immune-mediated adverse events have been shown to occur with immunotherapy and may cause disease through systemic immune activation, most symptoms are mild to moderate. Overall immunotherapy in advanced melanoma has provided effective and durable responses to treat patients with advanced melanoma.By augmenting preexisting antitumor immunity and preventing tumors from co-opting immune checkpoints, immunotherapy allows the immune system to destroy cancer cells.