Melanoma patients can be split into two main categories that have different aims for treatment; localised disease with either intermediate or high-risk of recurrence after surgery, and metastatic disease. Over the past decade, there have been many clinical trials looking at improving the success rates for localised and metastatic melanoma with alternative systemic treatments, namely immunotherapy, biochemotherapy and vaccines. This literature review summarises the clinical trials for each form of systemic treatment in localised and metastatic melanoma and assesses the effectiveness of each by an evaluation and comparison of relevant clinical trials for each systemic modality. The main objective was to assess whether alternative forms of systemic therapy have improved the disease free and overall survival rates achieved with chemotherapy.