Cutaneous malignant melanoma is the most aggressive skin cancer. It is also the most rapidly spreading cancer in terms of worldwide incidence. Although it is detected by simple inspection and can be relatively easily removed or treated, differential diagnosis to other melanocytic lesions, lack of prognostic markers, and no efficient treatment of advanced melanoma pose problems. Detection and targeting of proteases may represent a useful tool since they play a role in tumor cell metabolism, invasion, angiogenesis and metastasis. This review gives an overview of the role of proteases in development and progression of cutaneous malignant melanoma. In addition, regulation, activation, and interaction of proteases and their inhibitors are explained for tumors in general. The potential use of proteases as differential markers for melanoma mimicking melanocytic lesions, as biomarkers in tissues, and as prognostic serum markers is discussed. Current and future possibilities to target tumor proteases in therapy are presented.