Cysteine cathepsins are proteases critical in physiopathological processes and show potential as targets or biomarkers for diseases and medical conditions. The 11 members of the cathepsin family are redundant in some cases but remarkably independent of others, demanding the development of both pan-cathepsin targeting tools as well as probes that are selective for specific cathepsins with little off-target activity. This review addresses the diverse design strategies that have been employed to accomplish this tailored selectivity among cysteine cathepsin targets and the imaging modalities incorporated. The power of these diverse tools is contextualized by briefly highlighting the nature of a few prominent cysteine cathepsins, their involvement in select diseases, and the application of cathepsin imaging probes in research spanning basic biochemical studies to clinical applications.