Relegated to clinical afterthought, the topic of infection control has never taken center stage in our modern dental sedation and anesthesiology practices. Surgical and procedural masks, gloves, gowns, protective eyewear, and appropriate surgical attire have remained de rigueur in both fashion and custom for decades. However, the emergence of certain seminal events throughout health care history has driven mandated changes when practitioners, staff, patients, and the surrounding communities were exposed or put at risk of exposure to infectious disease. Hepatitis, human immunodeficiency virus, and now the global COVID-19 pandemic involving the novel coronavirus SARS-CoV-2, have forced us into rethinking our current practices. This review article will contextualize previous epidemics and their influence on infection control in dental settings, and it will explore the rapid evolution of current modifications to personal protective equipment and infection mitigation practices specific to sedation and anesthesia in dentistry.