Conservation, characterization and exploitation of agrobiodiversity are key factors to guarantee food security and face future challenges such as climate changes. These issues are the subject of a series of international agreements, such as the Convention of Biological Diversity, with its Nagoya Protocol, and the International Treaty on Plant Genetic Resources for Food and Agriculture (ITPGRFA) adopted in 2001 and entered into force in 2004. Italy ratified the Treaty in 2004 and instituted a long-lasting program, RGV-FAO, to implement it. CREA is one of the three organizations involved in the RGV-FAO Program, together with the National Research Council (CNR) and Reti Semi Rurali. CREA maintains a total of 40,186 accessions including cereals, vegetables, fruits, forages, industrial crops, forest and woody crops, medicinal and aromatic plants, and their wild relatives. Accessions are conserved using different ex situ conservation systems (seeds, in vivo plants, vegetative organs and in vitro plantlets), and characterized using genetic, morpho-phenological and/or biochemical methods. Herein, we will present the CREA long-lasting program RGV-FAO with some examples of the use of plant genetic resources in breeding programs, including molecular approaches. Some critical issues related to access and benefit sharing in PGRFA, such as the Nagoya Protocol and the Digital Sequence Information, will be discussed, highlighting their potential impact on food security and on the advancement of knowledge.