Enamel remineralization is generally studied in superficial (up to 100 μm) lesions, but in vivo caries lesions may be tenfold deeper. This article addresses the question whether deep lesions, and extending into dentine, can be remineralized under optimal conditions and if this process is influenced by agents affecting calcium phosphate precipitation and dissolution. Lesions through enamel into dentine were first formed in thin sections and then continuously remineralized for periods up to 200 days. With longitudinal assessment by transversal microradiography it was showed that remineralization throughout the depth of the lesion and into the dentine was possible, although this process is very slow. Fluoride and bisphosphonate treatments affected mainly the deposition in the outer enamel. Although it was assumed that this would affect the diffusion of ions to deeper layers, the treatments had no impact on remineralization in the inner enamel or dentinal parts of the lesions. These findings are discussed with relevant theoretical considerations, and in their possible clinical implications.