Statistical business registers play a central role in the production of business statistics, both in terms of the way the statistics are produced and in terms of the content and quality of the statistics. The availability and quality of statistical business registers are key to the compilation of consistent and comparable business statistics. Business registers are essential for establishing efficient statistical survey frames. A high-quality business register helps make national statistical systems more efficient and helps reduce the reporting burden on businesses. This 2021 edition of the European business statistics methodological manual for statistical business registers is an update of the 2010 Business Registers Recommendations Manual. It covers new developments and initiatives related to statistical business registers: the new Regulation (EU) 2019/2152 on European Business Statistics (the EBS regulation); the European Statistical System Vision Implementation Project on the European System of Interoperable Statistical Business Registers; the development of the Data Quality Programme for national statistical business registers; new operational rules for the implementation of statistical units.