It is predicted that in the 21st century there will be more and more new drug investments that violates the Lipinski's “rule-of-five”. Among them, peptides have received increased interest in the current drug therapies. Advantages of peptide-based pharmaceuticals are the high potency and selectivity as well as their low accumulation in tissues; thus, they have potentially lower toxicity than the small drug molecules. Furthermore, the high chemical and biological diversity of peptides provide a broad range of targets, which could represent a basis for personalized medication. Currently, there are more than 70 approved peptide drugs on the market, generating an annual sale close to USD 20 billion in 2012. About half of them are presented in this chapter, which ones are used for the treatment of diabetes, cancers, multiple sclerosis, HIV, hereditary angioedema, respiratory distress syndrome, prevention of thrombosis or relief pain. Next to the structures of the peptide-based pharmaceuticals, their biological activity on the mentioned diseases will be shortly discussed. An outlook for the new peptide-based drug development indicates high perspectives of this area.