In this paper, we review gene bank operations that have an influence on the global conservation system, with the intention to identify critical aspects that should be improved for optimum performance. We describe the role of active and base collections and the importance of linking germplasm conservation and use, also in view of new developments in genomics and phenomics that facilitate more effective and efficient conservation and use of plant agrobiodiversity. Strengths, limitations, and opportunities of the existing global ex situ conservation system are discussed, and measures are proposed to achieve a rational, more effective, and efficient global system for germplasm conservation and sustainable use. The proposed measures include filling genetic and geographic gaps in current ex situ collections; determining unique accessions at the global level for long-term conservation in virtual base collections; intensifying existing international collaborations among gene banks and forging collaborations with the botanic gardens community; increasing investment in conservation research and user-oriented supportive research; improved accession-level description of the genetic diversity of crop collections; improvements of the legal and policy framework; and oversight of the proposed network of global base collections.