The pharmaceutical market has largely been dominated by small molecule drugs; however, larger biomolecules have recently become important contenders. Of these biomolecules, protein and peptide therapeutics are proving useful due to their often improved pharmacokinetic properties. In many circumstances, functionalisation of the protein or peptide therapeutics results in performance enhancement, and various methodologies are applied. In addition, introducing unnatural amino acids for structural reinforcement via chemical modification is also common. These strategies are discussed in this review.