AbstractBackgroundInjective procedures using polynucleotides‐based products to promote dermal rejuvenation and revitalization are steadily evolving, yet no structured protocols are available that discuss and provide guidance in aesthetic treatments with highly purified polynucleotides. The goal of this document was to provide consensus‐based recommendations for the safe and effective use of Polynucleotides Highly Purified Technology™ (PN‐HPT™) devices for skin rejuvenation.Patients/MethodsA team of eight experts with extensive experience in treatments for skin rejuvenation and revitalization integrated the best available evidence and clinical judgment and devised a series of practical guidance to support dermatologists, plastic surgeons, and aesthetic physician in the use of PN‐HPT™ products, alone and in combination, in aesthetic medicine.ResultsFor most items, the expert group achieved a majority consensus. “Recommendations” (consensus >80%) were reached for the face, periocular area, décolleté and neck, hands, scalp, and stretch marks. Recommendations include details of techniques, information on dosage, volumes to be injected, and the ideal number of required treatment sessions, as well as time intervals between them for different areas of face and body. A lower agreement level of 60% was reached on but one item related to the initial treatment cycle for the face, leading to a “Consensus statement” for that area instead of a full “Recommendation.”ConclusionThe expert consensus illustrates the value of natural‐origin, highly purified polynucleotides (PN‐HPT™) as biostimulatory booster strategy for skin priming and revitalization of face and body and provides a detailed guide for the use.