Peptides are recognized for being highly selective and efficacious and at the same time relatively safe and well tolerated. Consequently, there is an increased interest in peptides in pharmaceutical R&D, and approximately 140 peptide therapeutics are currently being evaluated in clinical trials. As the low-hanging fruits in the form of obvious peptide targets have already been picked, it has now become necessary to explore new routes beyond traditional peptide design. Examples of such approaches are multifunctional and cell-penetrating peptides as well as peptide drug conjugates. Here, we discuss the current status, the strengths and weaknesses of peptides as medicines and the emerging new opportunities in peptide drug design and development.