Kallikreins are serine proteases that are traditionally linked to poor clinical prognosis of human carcinoma. The most popular is prostate specific antigen (PSA), also known as human kallikrein 3 (hK3) that serves as a diagnostic biomarker for prostate cancer. Serine proteases mediate substrate cleavage by histidine, serine and aspartic acid amino acids, which are usually close to one another and hKs additionally contain 10-12 cysteine residues. Tissue kallikrein gene (KLK) expression is highly regulated by sex-steroid hormones [ 15 ], like androgen regulation of KLK2 and KLK3 [ 56 ], but there are also post-translational regulations to control the irreversible protease action. Proteolytic activity of hKs can be inhibited by interactions with plasma globulin, serpins, tissue inhibitors, zinc ions [ 57 ] as well as by its own fragmentation [ 15 ]. The pro-enzyme can be activated by intracellular or extracellular hydrolysis or by other hKs [ 15 ]. Kallikreins are found in sweat, milk, saliva, seminal plasma and cerebrospinal fluid in humans because they are mainly secreted from epithelial cells in skin, breast, prostate, pancreas and brain. Under diseased conditions like cancer, hKs are dysregulated. In ovarian cancer, for example, twelve KLK genes are upregulated [ 15 ]. However, emerging data indicates that hKs can both promote and inhibit tumor progression and is most likely dependent on hormone balances as well as the tissue type. This also makes determining its substrate a challenge as it may be tissue specific [ 58 ]. Otin et al. discusses the tumor suppressing roles of hK3, hK8, hK9, hK10, hK13, hK 14 [ 2 ]. Yet, it is the overexpressed hKs in different cancers that can serve as viable targets for drug delivery.