The biodeterioration process involves every type of Cultural Heritage item, including monuments, stoneworks, frescoes, and easel paintings. The accurate study of the microbial and fungal communities dwelling on artworks, and involved in their deterioration, is essential for the adoption of optimal prevention and conservation strategies. Conventional restorative methods, that usually involve chemical and physical technologies, present some disadvantages, including short-term and unsatisfactory effects, potential damage to the treated works, human toxicity, and environmental hazards. Research in the field of restoration has paved the way for innovative biological approaches, or ‘biorestoration’, in which microorganisms are not only considered as an eventual danger for artworks, but rather as potential tools for restoration. The present review describes the main aspects of the biodeterioration process and highlights the most relevant biorestoration approaches: bioconsolidation, biocleaning, biological control, and new promising bio-decontaminating compounds.