Going beyond the simple understanding of the phenomena observed, often through serendipitous discovery, is still a generally open problem. Retrospective investigation of an unexpected behavior, either through advanced experimental techniques or molecular simulation at various scales, has become more common in the literature. On the other hand, examples of targeted prediction of a specific and desirable behavior, a priori, followed by synthesis and confirmation of the properties, are still relatively rare. The common intuition of researchers in the field is that it should be possible to design or engineer framework materials with targeted physical or chemical properties. The literature is brimming with analogies of this class of compounds, and especially of metal-organic frameworks, with everyday building systems and toys such as LEGO bricks or Tinkertoy construction sets. There are, however, limitations to that analogy bridging the macroscopic and microscopic scales: in particular, the self-assembled nature of framework materials means that it is difficult to predict which materials are experimentally feasible or synthetically accessible, and under what conditions.