Mycoplasma contamination constitutes a serious concern for cell culturists as these bacterial strains are a common cause of cell line contamination affecting roughly 15-35% of cell cultures and endangering almost all aspects of cell physiology. This is of particular concern for research laboratories and commercial facilities that employ cell lines in the development and manufacture of cell-derived biopharmaceutical products for medical use. Contamination of cell substrates used in the production of biopharmaceuticals poses a potential safety risk for patients and presents a serious economic risk for manufacturers in the event of batch adulteration or a product recall. To minimize these risks, routine testing for mycoplasma is performed throughout the product manufacturing and development process. In this article, we will discuss the effects of mycoplasma contamination, how this form of adulteration can affect cell-based drug development, and several quality control techniques and related products that can be used in the detection of mycoplasma contamination.