This chapter traces the ever-increasing market-approved biopharmaceutical portfolio. Although biological medicines have been developed over the past century (e.g., immune serums, vaccines), only in the last four decades have biopharmaceuticals started to enter the marketplace. From the 1980s through today, biopharmaceuticals have entered the marketplace in four major “waves.” The protein-based biopharmaceuticals were first—first wave recombinant proteins, second wave monoclonal antibodies, and third wave biosimilars. These protein-based biopharmaceuticals have all been manufactured by applying the Central Dogma of Molecular Biology: DNA → mRNA → amino acid (protein). Through genetically engineering of living microorganisms, biopharmaceuticals are manufactured on a large scale in bioreactors, which then require purification. While the number of recombinant proteins, monoclonal antibodies, and biosimilars continues to grow (over 300 products market-approved to date), there is heightened interest in various derivatives of the monoclonal antibodies (e.g., bispecific antibodies, antibody-drug conjugates). The fourth wave of biopharmaceuticals—gene-based biopharmaceuticals (i.e., viral and non-viral vectors, genetically modified patient cells)—has begun to penetrate the marketplace. These gene-based biopharmaceuticals also apply the Central Dogma of Molecular Biology: DNA → mRNA → amino acid (protein), but the twist is that the manufacture of the desired medical protein is done inside the human patient. Now, the human patient is the “bioreactor.”