Senolytics are a new class of anti-aging drugs developed to selectively kill ‘senescent’ cells that are considered harmful in normal aging. More than twenty drug trials are ongoing with diverse ‘senolytic cocktails’. This commentary on recent reviews of senolytics gives historical context of mammalian cell senescence that enabled these new drugs. While cell senescence is considered harmful to aging tissues, many studies show its essential role in some regenerative and developmental processes for which senolytic drugs may interfere. Longer-term studies of side effects are needed before senolytics are considered for general clinical practice. The wide occurrence of cell senescence in eukaryotes, yeast to fish to humans, and suggests an ancient eukaryotic process that evolved multiple phenotypes.