Biologicals or biologics are complex molecules derived from living cells. They include vaccines, therapeutic sera, toxins, antitoxins, blood and blood products, allergenic extracts, monoclonal antibodies, human cells and tissues used for transplantation, gene therapies, and cellular therapies. Since the development of recombinant insulin “humulin” as the first genetically engineered biological medicinal product, they have revolutionized the treatment of many diseases including cancers as targeted therapies. Currently, there are well over 500 biological drugs available worldwide, with many of the top-selling drugs being biologics. However, their manufacture and development are complex, and they are much more expensive than conventional drugs. “Biosimilars” are generic or alternate versions of biologicals that have come off-patent, having quality, biological activity, safety, and efficacy comparable to an approved biological. They offer the advantages of lower development cost, lesser development period, and increased accessibility. There are well-defined determinants of similarity and interchangeability. In the last two decades, the regulatory agencies across the world have released thorough guidance for rational and scientific development of biologicals and biosimilars. Together, they are fast changing the landscape of modern therapeutics, as “lifesaving” medicines, as well as paving the way for personalized medicine.