When formulating a tablet, the solubility of the tablet matrix is often used as the sole criteria for disintegrant selection. Most formulators tend to select swelling-type disintegrants for insoluble matrices and wicking-type disintegrants for soluble matrices. This executive summary presents an in-depth analysis of the effects of disintegration mechanisms, pH of test media, matrix plasticity, tablet hydrophobicity, and storage effects on the disintegration behavior. In addition, the interaction of disintegrants in the tablet surface with environmental humidity is taken into consideration as an additional element for rational excipient selection.