Plant survival in natural communities depends on the outcome of positive and negative interactions with neighboring plants, microbes, animals and the environment. The Allelopathy hypothesis describes the real meaning of secondary metabolites as a tool of immobile plants to protect themselves from surrounding plants or other life that might attack them, or a tool to communicate each other or to communicate with other life for their survival. The practical use of natural compounds as control agents is receiving increased attention and this is partly due to their non-toxicity to humans, their systemicity and biodegradability. Selection of allelopathic plants is a good and commonly used approach for identification of plants with biologically active natural products. Allelochemicals are often identified by testing for phytotoxicity under controlled conditions of a given chemical found in the plant or associated soil. It would be necessary to initiate the studies from crude extracts with targeted isolation of responsible allelochemicals in plants. Recently, both the necessity of field validation of allelopathy and novel weapons and the use of rigorous analytical chemistry methods to quantify field bioactive concentrations of putative allelochemicals have been raised. Natural compounds have been developed as natural plant protectants. These approaches are promising to reduce human dependency on synthetic chemicals to overcome plant biotic and abiotic stresses.