Recent advances in quadrupole TOF (Q-TOF) MS have some bioanalytical scientists referring to a 'paradigm shift' in their field. They are speaking of a potential move away from workflows based upon triple-quadrupole MS. Gone would be the optimizing of numerous parameters in selected-reaction monitoring (SRM) experiments, replaced with more generic workflows provided by Q-TOF instruments with high data acquisition rates, excellent mass accuracy (≤5 ppm) and high resolving power (≥30,000). Such a move could pay real dividends for high-throughput workflows, especially in drug metabolism and pharmacokinetics analyses where quantitation and qualification studies could actually be merged. But, are modern Q-TOF-MS instruments, touted as high-resolution MS, ready for this? If not, how close is it? This article will examine these questions by reviewing recent advances in Q-TOF technology and some fascinating orthogonal technology (such as ion mobility) that modern Q-TOFs employ for even greater analytical power.