All biomaterials used in dentistry must be evaluated for biocompatibility using screening assays to protect patient health and safety. The purpose of this review is to explain the international biocompatibility guidelines, and to explain the structure of a test program. The test program requires the structured assessment of materials into four phases; general toxicity, local tissue irritation, pre-clinical, and clinical evaluation. Different types of screening assays are available, and it is important to understand the advantages and limitations of the various types of assays that are available, so that they can be selected for appropriateness and interpreted accurately. New scientific advances in terms of the chemical properties of dental materials, tissue engineering, stem cell, genetic transfer, biomaterial, and growth factor therapies are under development. These new therapies create improved opportunities to restore and regenerate oral tissues, but they can also present new hazards to patients. Prior to their clinical use, these new technologies must be proven to be safe, and not hazardous to human health. A structured biocompatibility assessment and advice on the selection of assays are outlined to evaluate these new therapies.