Cathepsins are a diverse group of lysosomal proteases that function as both endopeptidases and exopeptidases, and they are present in various cell types throughout the body. There are 15 different cathepsins, which are classified into three families based on the nucleophilic residue at their active sites: serine proteases (cathepsins A and G), aspartate proteases (cathepsins D and E), and cysteine proteases (cathepsins B, C, F, H, K, L, O, S, V, W, and Z). Each cathepsin exhibits unique reactive-site properties and tissue-specific expression patterns, which are regulated by a complex interplay of their expression, activation, inhibition, and degradation. These enzymes are indispensable for various physiological processes such as immune regulation, autophagy, cell death, and bone remodeling. Cathepsins dysregulation can lead to pathological consequences, including extracellular matrix degradation, autoimmune disorders, tumor progression, cardiovascular diseases, and neurodegeneration. Despite extensive research into their classification, pH-dependent activity, and functional roles, many aspects of cathepsin biology remain unclear. This chapter highlights the biochemical characteristics, physiological relevance, pathological roles, and therapeutic potential of cathepsins, emphasizing their importance in both health and disease.