Since the discovery of the critical role of cathepsin K in bone resorption, cysteine cathepsins have been investigated by pharmaceutical companies as drug targets. The first clinical results from targeting cathepsins by activity-based probes and substrates are paving the way for the next generation of molecular diagnostic imaging, whereas the majority of antibody-drug conjugates currently in clinical trials depend on activation by cathepsins. Finally, cathepsins have emerged as suitable targets for targeted drug delivery. Focus will be on cathepsins in inflammation-associated diseases, because dysregulation of the immune system where elevated cathepsin activity contributes to disease progression is a common feature of these diseases.