There have been numerous reports demonstrating that polysaccharides contained in the gel of aloe species exhibit immunomodulatory activity in vivo as well as in vitro. Studies on the efficacy and toxicity of the aloe polysaccharides have even lead to the development of an injectable form of polysaccharide, acemannan (CARN 750). The mechanisms for the immunomodulatory activity has become clearer in recent years. The fact that acemannan induces phenotypic and functional maturation of immature DCs has an important implication in understanding the antiviral and antitumoral activities of acemannan, because it has been well-documented that DCs are the most important accessory cells for the activation of naïve T cells and generation of primary T cell responses. Although there is a general consensus on the diverse immunomodulatory activities of the polysaccharide fraction isolated from aloe gel, the optimal molecular size exhibiting maximum immuno-modulatory activity has been a matter of debate. Optimal molecular size exhibiting maximal immunomodulating activity may vary depending on the examination parameters for the immunomodulatory activities. Examination of the molecular size-activity relationship showed that polysaccharides between 5 – 400 KDa exhibit the most potent immunomodulatory activity. The fact that MAP smaller than 400 KDa exhibits potent immunomodulatory activity has important implications, because, for in vivo applications, smaller MW molecules are usually preferred to higher MW molecules due to bioavailability issues. Further studies using different in vivo systems are still required to establish the molecular size-activity relationship more clearly, and this type of study would be essential to develop aloe polysaccharides as therapeutic drugs.