Selective targeting of senescent cells has been thus far considered a widespread preventive strategy, as well as a main or adjuvant therapy for age-associated diseases, fueling the research on the discovery of senotherapeutics (i.e., senolytic or senomorphic compounds). Given that until now no single senotherapeutic has been reported to exert a universal anti-senescence action due to the cell- /tissue-, and context-dependent specificity of such compounds, seeking novel selective senotherapeutics remains of great importance. In this chapter, a research strategy that could be followed to screen natural product collections for putative senotherapeutics with enhanced specificity and reduced toxicity is presented, from the extraction of the source material and the isolation and chemical characterization of the compounds of interest to their biological evaluation in vitro and in vivo.