Proteolytic activity is required for several key pro-tumorigenic processes: angiogenesis, invasion and metastasis. Consequently, increases in protease expression and activity are frequently reported in human cancers, and correlate with malignant progression and poor patient prognosis. Cysteine cathepsin proteases have recently emerged as an important class of proteolytic enzymes in cancer development, and cysteine cathepsin inhibitors have been proposed as anticancer agents. In this review, we highlight recent studies that now allow us to evaluate critically whether cysteine cathepsin inhibition represents a viable therapeutic strategy for the treatment of cancer.