The ethical-legal framework of research biobanking activities is still scarcely defined in Italy, and this constitutes a major obstacle to exploit the potential benefits of existing bioresource patrimony at the national and international levels. Biobanking and Biomolecular Resources Research Infrastructure (BBMRI), which aims to become a major interface between biological samples and data and top-level biological and medical research, is undertaking the crucial transformation to the ERIC (European Research Infrastructure Consortium) legal entity. In this scenario, there is a need to address the national legal and ethical concerns that are strictly correlated with the use of human biosources in research across European countries participating (and not) in BBMRI. In this perspective, this article aims to review the legal framework applying to research biobanking in Italy, including both "soft" nonbinding instruments and binding regulations. Since ethical and societal aspects impact biobanking research activities, the article discusses both the critical ethical and legal open issues that need to be implemented at the national level.