Recombinant technology has ushered in a new era for the pharmaceutical industry. Protein therapeutics, including plasma-derived products and antibodies obtained from the serum of infected patients, have been successfully adopted and utilized to treat various indications. The development of recombinant technology and the subsequent improvement in expression, purification, and formulation technologies have enabled the generation of highly purified proteins in a scalable and cost-effective manner. The discovery and development of several recombinant proteins, such as growth factors and cytokines, will be described followed by a brief review of monoclonal antibodies and enzyme replacement therapy. Recombinant protein-based vaccine, which is the focus of the current review, is described in detail with particular emphasis on several viral and bacterial infections. Challenges and new approaches in their use as a replacement for the currently available vaccines are discussed.