Natural exogenous immunostimulators are preparations isolated from bacteria, plants or fungi that activate immunological system. Present research is aimed at understanding the exact mechanism of their action and improving their efficacy in parallel with reducing minor side effects. It appears that in the majority therapeutical effects of the bacterial and fungal preparations result from the activation of Toll- like receptors (TLR). However, biologically active substances isolated from plants can activate cells through non-specific interaction with their surface. In the present work, the most important biologically active compounds were discussed: bacterial – BCG, LPS; isolated from plants – purple coneflower (Echinacea spp.), mistletoe (Viscum album); and fungal – lentinan, schizophyllan, krestin. The mode of their actions with both the present and potential therapeutic applications were discussed. Among groups mentioned above, the most commonly used in medicine are BCG and purple coneflower preparations. BCG is applied in the treatment of superficial bladder cancer. Anticancer effect of BCG results from either eliciting local inflammation or cross-reaction of antibodies specific for BCG with bladder tumor cells. As far as purple coneflower and biologically active substances isolated from the plant are concerned, they have immunostimulating properties because of their effect on non-specific immune response and can act in the antiseptic and antiinflammatory way. The immunostimulating properties of other preparations are generally low. The preparations can be used occasionally as a supplement of the conventional therapy.