As the virtual libraries have grown from millions to billions of compounds, the practical issues with enumerated compound libraries have become apparent to the computational drug hunters. Even the simple 1D-SMILES representation of molecules can take hundreds of gigabytes of space, making the storing and updating of these enumerated libraries non-trivial and time consuming. One solution to the issue is to describe the virtual libraries as collections of building blocks. These are then connected with specific rules forming the final molecules. Thus avoiding the combinatorial explosion. For example, by using the space-file format developed by BioSolveIT, the 48-billion-compound Enamine REALSpace takes just half a gigabyte of disk space.