The population of the developing world rely ~ 70 - 90% on traditional medicines for primary health care. Herbaceous rhizomatous plants that belong to the Zingiberaceae ginger family have been used throughout Asia and India for traditional medicine applications for centuries. In Indonesia Curcuma xanthorrhiza, also known as 'temu lawak', is used for its curcumin extract in traditional medicine applications. These traditional medicine applications as a whole are referred to as 'JAMU'. In Ayurvedic traditional medicine, practitioners utilize 'HALDI' (Hindi) as an ailment and tonic and remedy and Southern Asia uses 'JIANG HUANG' as a treatment for digestive and liver complications. There are approximately 130 species of Curcuma (collectively referred to as curcuminoids) and in particular, C. longa (turmeric), C. aromatica (wild turmeric), and C. xanthorrhiza (Javanese turmeric), have all been used for the maintenance of good health and the management of disease. Curcumin is a natural polyphenol, known as diferuloymethane, and is a major active constituent produced primarily in the rhizomes of the plant root system. Despite the longstanding traditional medicine applications, a total comprehensive understanding of the therapeutic actions and health benefits of curcumin remain unknown. The medicinal properties of curcumin are several fold and include relief of inflammatory conditions, digestive disorders, arthritic and skin conditions, cancers and neurodegeneration, to name a few. Various studies have shown that curcumin can modulate numerous targets such as cytokines, enzymes, growth factor receptors, transcription factors, and genes that regulate apoptosis. However, the biological mechanisms involved during these processes remain mostly unidentified. In this chapter, we discuss some of the known molecular targets and biological mechanisms of curcumin. In particular, an emphasis on the neuroprotective effects of curcumin via its influence on toxic catabolites, such as N-methyl-D-aspartate (NMDA) receptor agonist, excitotoxin quinolinic acid (QUIN) and the kynurenine pathway, are also discussed.