Although the use of fluorides has been successful in reducing dental caries, the need remains to develop and evaluate new approaches and promising products for caries prevention. Comprehensive caries-prevention protocols should encompass fluoride and other agents affecting the de-/remineralization balance but also antimicrobial strategies. Different from the traditional restorative approach, the current opinion is that caries should be detected and monitored in its earliest stages, when a nonsurgical reversal can still be achieved. This paradigm shift has implications for methods of caries diagnosis, the choice of preventative materials and the design of randomized clinical trials. This article summarizes the highlights of a special conference dedicated to the topic of novel anticaries and remineralizing agents (ICNARA 2), and identifies the current consensus and remaining questions on pivotal issues in this field.