The contribution of applied microbiology and biotechnology for the preservation and restoration of culturally relevant stoneworks has been used only to a minor extent. Until recently it only involved the identification of the living organisms accountable for the deterioration of those materials by classic phenotypic identification methods. This seems to be changing, given the amount of work recently published that focuses in the introduction of molecular-based techniques for the detection of microorganisms in historic stone. Such techniques complement and expand the information up till now gathered by conventional identification methods. Along with this, efforts are being made to develop and implement bio-based methodologies that may actively contribute to the bioremediation of weathered historic stoneworks. The present mini-review aims to provide an overview of recent findings on these matters.