The ultimate goal of a regenerative pulp treatment strategy is to reconstitute normal tissue continuum at the pulp-dentin border, regulating tissue-specific processes of tertiary dentinogenesis. Experimental investigations in mature teeth have shown that a network of extracellular matrix molecules and growth factors signal tertiary dentinogenesis. Application of dentin matrix components or growth factors in deep dentinal cavities stimulated up-regulation of biosynthetic activity of primary odontoblasts (reactionary dentin formation). Pulp-capping studies with a broad spectrum of biological agents, including growth factors and extracellular matrix molecules, showed formation of osteodentin and/or tertiary dentinogenesis (reparative dentin formation). Promising biologically active substances should be subjected to careful evaluation in well-designed preclinical investigations as well as in long-term clinical trials before their introduction in clinical practice.