The powdered rhizome of turmeric has been extensively used in India and other South Asian cuisines, and is an integral part of Ayurvedic medicine for a broad range of conditions. In particular, curcumin, a major active component of turmeric, is one of the most studied botanicals for its anti-inflammatory, anti-oxidant and anti-cancer properties. Despite its well-documented therapeutic efficacy, for years the limited systemic bioavailability of curcumin has hindered its development as a potential therapeutic agent. However, recent introduction of unique extraction processes and various delivery methods has resulted in the development of new curcumin formulations and significantly improved its bioavailability. While these new formulations will no doubt expand curcumin's therapeutic potential, there are notable inconsistencies surrounding curcumin's bioavailability and corresponding bioactivity, raising some important questions. This article dissects various contributing factors of curcumin bioavailability to identify possible causes for the discrepancies associated with its bioactivity and discuss how these new curcumin formulations could further improve its clinical usefulness.