ΚΒ3-1 cells selected for resistance to paclitaxel in the presence of a P-glycoprotein reversal agent display a mutation in β.-tubulin at Asp26Glu. Computational modeling associated with the single point mutation in tubulin is consistent with differing resistance observed between paclitaxel and other taxanes as depicted by detailed interaction models of paclitaxel and docetaxel in wild type β.-tubulin (top) and paclitaxel in Asp26Glu mutant β.-tubulin (bottom). In this issue, Hari and coworkers consider the resistance as a function of both impaired drug binding and microtubule instability.