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Searching for drugs that extend healthy lifespan and the subsequent analysis of their mechanisms of action is a crucial aspect for aging research. However, identifying both longevity-enhancing drugs and their corresponding targets is challenging. The roundworm Caenorhabditis elegans is a suitable model for such research because of its short lifespan and genetic tractability. In this perspective, we discuss recent progresses on the identification of anti-aging drugs and characterization of their targets using C. elegans as a model organism. In particular, minocycline, JZL184, monorden, and paxilline increase C. elegans lifespan by inhibiting 18S rRNA/ribosome, fatty acid amide hydrolase-4, Hsp90, and the Ca2+-activated K+ (BK) channel SLO-1, respectively. Because many factors that regulate aging and lifespan in C. elegans are evolutionarily conserved, these newly identified lifespan-extending compounds may guide the development of anti-aging medicines for humans. Keywords: Caenorhabditis elegans, Aging, Healthspan, Lifespan, Drug