Image-guided laser ablation systems are now feasible for dentistry with the recent development of nondestructive high-contrast imaging modalities such as near-IR (NIR) imaging and optical coherence tomography (OCT) that are capable of discriminating between sound and demineralized dental enamel at the early stages of development. Our objective is to demonstrate that images of demineralized tooth surfaces have sufficient contrast to be used to guide a CO2 laser for the selective removal of natural and artificial caries lesions. NIR imaging and polarization-sensitive optical coherence tomography (PS-OCT) operating at 1310-nm are used to acquire images of natural lesions on extracted human teeth and highly patterned artificial lesions produced on bovine enamel. NIR and PS-OCT images are analyzed and converted to binary maps designating the areas on the samples to be removed by a CO2 laser to selectively remove the lesions. Postablation NIR and PS-OCT images confirmed preferential removal of demineralized areas with minimal damage to sound enamel areas. These promising results suggest that NIR and PS-OCT imaging systems can be integrated with a CO2 laser ablation system for the selective removal of dental caries.