The emergence of recombinant DNA technology has resulted in the large-scale production of a myriad of genetically engineered proteins and peptides, making many of them available for the first time for potential use as therapeutic entities. In addition, increased knowledge in the area of peptide/polypeptide hormones has resulted in an expansion of research efforts utilizing peptide synthetic chemistry, aimed toward developing novel therapeutic peptide drugs. Proteins and peptides cannot readily be administered by the conventional oral route, and thus alternative delivery methods to circumvent the necessity of frequent injections are being explored. This article reviews the current state-of-the-art technology of such methodologies, encompassing localized administration, administration to various body cavities (i.e., nasal, rectal, etc.), as well as controlled-release injectable or implantable systems. These different approaches result in quite different pharmacokinetics that may in part dictate which approach is best suited for a particular protein or peptide.