For 5,000 years innovative researchers, often anonymously, have been providing dentists and their antecedents with a rich inheritance of information, techniques, and materials. The giants of dental research of the past can still serve as role models today. This paper presents a history of clinical research and relates past work to current and future trends. In the last few decades, both technical innovation and oral biology and prevention have been progressing at an accelerated rate to provide a steady influx of new answers to dental practitioners and to elicit new questions from the next generation of dental investigators.