Clarity around the intended definitions of isostructurality in solid forms is highlighted with respect to the pharmaceutical industry and the patenting of crystalline forms. The analysis of structural similarity is a difficult problem and especially so when additional components are included such as counterions in salt forms. In this study we investigate the structural similarity of sodium and potassium salts using a range of methods. It is clear that for this type of multi-component system, where one or more components change between forms, PXRD similarity is not sufficient to determine isostructurality, and careful examination of the 3D crystal structure coordinates is needed. Substantial and unpredictable changes in physical properties have been observed for even small deviations away from isostructurality. Finally, it is noted that sodium salt hydrates tend to exhibit a greater hydration level than potassium salt hydrates, and this trend is hypothesised to be due to the differing solution behaviour of the two cations.