The microtubule-stabilizing drug paclitaxel is a cytotoxic agent widely used for the treatment of a variety of tumor types. Since its introduction to the clinic, modifications to the administration schedule and treatments for hypersensitivity reactions and neutropenia have significantly improved paclitaxel therapy. On the other hand, severe neurotoxicity and lack of response are still clinical challenges. During the last decade a deeper knowledge of paclitaxel pharmacokinetics and pharmacodynamics has been achieved, together with an in-depth characterization of genes involved in its elimination and therapeutic response. Pharmacogenetic studies aimed at the identification of paclitaxel outcome biomarkers have been performed, however, further efforts will be required to successfully integrate these and future results to provide the basis for personalized paclitaxel therapy.