In recent years, biotechnologically derived peptide and protein-based drugs have developed into mainstream therapeutic agents. Peptide and protein drugs now constitute a substantial portion of the compounds under preclinical and clinical development in the global pharmaceutical industry. Pharmacokinetic and exposure/ response evaluations for peptide and protein therapeutics are frequently complicated by their similarity to endogenous peptides and proteins as well as protein nutrients. The first challenge frequently comes from a lack of sophistication in various analytical techniques for the quantification of peptide and protein drugs in biological matrices. However, advancements in bioassays and immunoassays-along with a newer generation of mass spectrometry-based techniques-can often provide capabilities for both efficient and reliable detection. Selection of the most appropriate route of administration for biotech drugs requires comprehensive knowledge of their absorption characteristics beyond physicochemical properties, including chemical and metabolic stability at the absorption site, immunoreactivity, passage through biomembranes, and active uptake and exsorption processes. Various distribution properties dictate whether peptide and protein therapeutics can reach optimum target site exposure to exert the intended pharmacological response. This poses a potential problem, especially for large protein drugs, with their typically limited distribution space. Binding phenomena and receptormediated cellular uptake may further complicate this issue. Elimination processes-a critical determinant for the drug's systemic exposure-may follow a combination of numerous pathways, including renal and hepatic metabolism routes as well as generalized proteolysis and receptor-mediated endocytosis. Pharmacokinetic/pharmacodynamic (PK/PD) correlations for peptide and protein-based drugs are frequently convoluted by their close interaction with endogenous substances and physiologic regulatory feedback mechanisms. Extensive use of pharmacokinetic and exposure/response concepts in all phases of drug development has in the past been identified as a crucial factor for the success of a scientifically driven, evidence-based, and thus accelerated drug development process. Thus, PK/PD concepts are likely to continue and expand their role as a fundamental factor in the successful development of biotechnologically derived drug products in the future.