Microglia, the brain’s immune cells, play vital roles in clearing toxins and maintaining neuronal health but can also contribute to neurodegenerative diseases if overactive. New research reveals sex-based differences in how adult male and female microglia respond to the enzyme inhibitor PLX3397, a common tool in microglial research. While male microglia showed the expected depletion, female microglia employed alternative signaling pathways, leading to increased survival.