Silicone sealants are widely used in building construction. Regardless whether the sealant is used in structural sealant glazing or in non-structural applications (such as weather-sealing joints), good adhesion of the silicone sealant to the building substrate is a prerequisite for good performance and long service-life (durability). Although silicone sealants typically show excellent unprimed adhesion to most building substrates, poor results have been reported occasionally, especially when sufficient care is not taken in substrate preparation. However, very occasionally, poor adhesion is observed, despite proper cleaning and priming of the substrate. Based on several years of work experience gained from laboratory testing and results obtained on thousands of substrate samples used for job site qualifications as well as from field performance inspections, the authors summarize important factors, which affect silicone sealant adhesion. These factors include sealant formulation, surface characteristics of the substrate, the effectiveness of the cleaner in removing surface contamination, et cetera. The authors' intention with this paper is to discuss each of these effects separately and to provide the sealant manufacturer and end user with useful information on how to avoid adhesion problems.