The ability of the extended similarity indices of requiring O(N) operations to compare N objects makes them immediately attractive to explore large sections of chemical space, potentially dealing with numbers of molecules out of reach for current approaches. The first direct application related to this is quantifying the chemical diversity of large molecular libraries. The key insight here is that while raw similarity values can be hard to interpret (except in the trivial cases when they are 0 or 1), we can easily determine the relative degree of diversity with respect to a given reference dataset.