Use of natural products as therapeutics, has been in practice even before the advent of modern medicine. Traditional medicinal systems like Ayurveda, Siddha and Unani which prescribe medicines based on natural products have been in practice for centuries, authenticating the medicinal efficacy of these drugs. However, with the advent of modern medicine, the focus shifted from medicines based on formulations to mostly single component drugs. Also, norms were established to standardize methodologies for clinical trials that will establish safety and efficacy of the drugs before human use. These stringent norms meant that most of the traditional medicines could not be used in the current medicinal system of treatment as drugs. Nevertheless, researchers have repeatedly mined these traditional natural sources and other similar materials for compounds with potential therapeutic value. Such research has yielded compounds like acetylsalicylic acid (aspirin), morphine, quinine and even Nobel prize winning natural products like artemisinin (anti-malarial agent) and avermectin (antibiotic). In fact, more than half of the drugs approved by FDA have either direct or indirect inspiration from natural products. Apart from these, several interesting natural products are also under various stages of clinical trials varying from inflammation, infection to dietary supplements. The present chapter reviews some of these attractive natural products namely curcumin, camptothecin, astaxanthin, and biochanin that are currently under various stages of clinical trials for their application as therapeutics in various diseases. The chapter also deals with challenges such as lead optimization, formulations and delivery systems that should be addressed by researchers to move the natural product from the realm of nutraceuticals to the area of clinical medicine.