For hundreds of years natural compounds have been used in herbal medicine. They have been known for their antibacterial, antifungal, anticancer activities as well as for enhancing wound healing and improving immunity. Recently growing interest in natural compounds has been observed, due to their ability to modulate cellular senescence. Particularly interesting are these compounds that can induce tumor senescence, delay senescence of normal cells or reverse changes associated with senescence - acting as "rejuvenation" agents. It has been shown that some of the natural compounds can both promote senescence of tumor cells as well as prevent it in normal cells. Thus, they can be useful in therapy of age-related diseases. Natural compounds can regulate nutrient and energy sensing signaling pathways that are involved in senescence. They can also influence the synthesis of reactive oxygen species, secretion of cytokines, telomere shortening or epigenetic changes of DNA. Natural agents often act in a pleiotropic manner. They can modulate cellular senescence in many ways e.g. by direct neutralization of free radicals and affecting other regulatory signaling pathways. Furthermore natural compounds, commonly used for years e.g. as spices, usually don't have any side effects. Therefore their use as dietary supplements or in long term therapy appears to be relatively safe.