BACKGROUND The major mechanism of action of antitumor taxanes, including two clinically useful antitumor agents, paclitaxel and docetaxel, lies in their interactions with β-tubulin in microtubule polymers, leading to cell cycle arrest and apoptosis. However, owing to the technical limitations, the molecular interactions of ligands with the residues in taxane binding sites of tubulin as well as the conformations adopted by taxanes on binding are still not fully understood. OBJECTIVE This review focuses on the exploration of paclitaxel's interactions with tubulin, and the impact of such efforts on the drug discovery for new taxanes and microtubule stabilizing agents (MSAs). METHODS Data were identified through the search of Chemical Abstracts and PubMed databases for research articles and reviews up to April 2008. CONCLUSION Based on a collection of information gathered from crystallography, 1D and 2D NMR spectroscopy (NOESY, ROESY, REDOR), and structural-activity relationship (SAR) by chemical synthesis and pharmacological assays, 'opened' or T-shape conformations have been predicted to be the biologically active ones in recent years, and confirmed by further SAR studies. Some more potent analogues than paclitaxel or simplified compounds with similar potencies to that of paclitaxel have been discovered. Structural studies of taxol analogues will continue to make great contributions to the rational design of taxanes and novel prototype MSAs for drug discovery.