Regulations and guidelines governing the use of animals in research require minimization of pain and distress. However, pharmacologic treatments to prevent or alleviate pain can interfere with the disease process being modeled. This presents a challenge to the veterinary and investigative staff in determining how to best optimize both animal comfort and research results. An important component of this decision making process receives comparatively little consideration: the impact of unalleviated pain on that same disease process. In this talk, we will discuss possible interactions of analgesics and unalleviated pain and how this may affect whether certain treatments are recommended, contraindicated, or perhaps without impact in various research models.