Spirulina is free-floating filamentous microalgae growing in alkaline water bodies. With its high nutritional value, Spirulina has been consumed as food for centuries in Central Africa. It is now widely used as nutraceutical food supplement worldwide. Recently, great attention and extensive studies have been devoted to evaluate its therapeutic benefits on an array of diseased conditions including hypercholesterolemia, hyperglycerolemia, cardiovascular diseases, inflammatory diseases, cancer, and viral infections. The cardiovascular benefits of Spirulina are primarily resulted from its hypolipidemic, antioxidant, and antiinflammatory activities. Data from preclinical studies with various animal models consistently demonstrate the hypolipidemic activity of Spirulina. Although differences in study design, sample size, and patient conditions resulting in minor inconsistency in response to Spirulina supplementation, the findings from human clinical trials are largely consistent with the hypolipidemic effects of Spirulina observed in the preclinical studies. However, most of the human clinical trials are suffered with limited sample size and some with poor experimental design. The antioxidant and/or antiinflammatory activities of Spirulina were demonstrated in a large number of preclinical studies. However, a limited number of clinical trials have been carried out so far to confirm such activities in human. Currently, our understanding on the underlying mechanisms for Spirulina's activities, especially the hypolipidemic effect, is limited. Spirulina is generally considered safe for human consumption supported by its long history of use as food source and its favorable safety profile in animal studies. However, rare cases of side-effects in human have been reported. Quality control in the growth and process of Spirulina to avoid contamination is mandatory to guarantee the safety of Spirulina products.