To obtain market approval from a regulatory authority for a new medicine, manufacturers must first initiate and then complete human clinical trials. Each regulatory authority has a prescribed regulatory pathway for initiating the clinical trial, for maintaining the clinical trial during its development, and then for seeking market approval. But not all pathways are the same or appropriate for all types of biopharmaceuticals, even within the same regulatory region. In this chapter, the pathways for regulatory approval specific to all biopharmaceutical types (recombinant proteins, monoclonal antibodies, biosimilars, viral and non-viral vectors, genetically modified patient cells), both within the United States (regulated by the US FDA) and the European Union (regulated by EMA), are discussed in detail. The enhanced challenge of introducing biopharmaceutical products in other countries (i.e., the rest of the world) is viewed. Similarities and differences in the CMC regulatory compliance requirements in these pathways as applied to biopharmaceuticals are examined.