Cellular senescence (CS) is considered an important mechanism to prevent malignant transformation of potentially mutated cells but, persistence of senescent cells within tissues alters microenvironment in ways that can promote cancer and aging phenotype thus underlining pathophysiologic processes of different age-related diseases. Coincident with this increased knowledge, understanding and finding modulators of the dynamics that control senescent-cell formation, fate and subsequent effect on tissue function has gained critical interest in experimental gerontology and cancer research. The purpose of this review is to discuss the evidence that various dietary bioactive compounds can modulate cellular senescence “in vitro” and to summarize findings and mechanisms that might be useful for the development of health-promoting nutraceuticals. An overview of cellular senescence and its impact in aging and cancer is described along with the strategies and pathways that are currently being investigated to target cellular senescence. Particular emphasis is given to the mechanisms by which bioactive dietary factors (i.e. most polyphenols) can delay or induce cellular senescence “in vitro” and how this knowledge could be used to explain the opposite effects shown in cancer lines and primary cells by some of these compounds. In addition, the problems to translate findings from modulation of cellular senescence “in vitro” into experimental treatments or clinical trials able to prevent or counteract age-related diseases are briefly described. The information herein provided might be useful to design further research in the field as well as to develop new nutraceuticals to be tested in experimental models and clinical trials.