Proteolysis is doubtlessly the most widespread mechanism of biological regulation. By controlling protein synthesis, turnover and activity, it is involved in fundamental physiological processes including apoptosis, cell differentiation, growth and signaling, fertilization, immune response, blood coagulation and digestion. Yet, uncontrolled proteolysis can be harmful for organisms, causing - amongst others - such diseases as cancer, emphysema, inflammation, and neurodegenerative, immunological, and cardiovascular disorders. This paper briefly describes recent advances in the development of methodological design to follow up protease activity. Novel methods of protease sensing are described and evaluated. A variety of fluorescent reporter molecules including nanoparticles, and rare metal chelates are also characterized.