Virtual library size has significantly expanded with "make-on-demand" virtual libraries. These libraries of readily synthesizable molecules combine hundreds of relatively simple reactions and hundreds of thousands of building blocks. For instance, the enumerated Enamine REAL database has gone from 1.95 billion molecules (May 2021) to over 6 billion molecules (Jan 2024). Concurrently, the unenumerated Enamine REAL space has increased from 19 billion molecules to 38 billion molecules.