Metastatic malignant melanoma is an incurable disease with a median survival of 8.5 months and a probability of surviving 5 years after the diagnosis of less than 5%. To date, no systemic therapy has meaningfully changed these survival end points. Currently, in the USA the FDA has approved three agents for the treatment of metastatic melanoma: hydroxyurea, dacarbazine and interleukin-2. None of these have demonstrated a meaningfully prolonged survival of patients with metastatic melanoma. Therefore, a number of innovative therapeutic strategies have been pursued to improve outcomes, including immune therapy, tyrosine kinase inhibitors and angiogenesis inhibitors. Herein, we review some of the recent advances in novel therapeutic developments for the treatment of metastatic melanoma.