Tissue-resident macrophages, such as the microglia in the central nervous system (CNS), are found in many vertebrate tissues. However, little is currently known about how populations of such macrophages are established and maintained. Although the transmembrane cationic amino acid transporter slc7a7, which is known to be required for the presence of microglia in zebrafish, was originally thought to be expressed in microglial precursors before entering the brain, Philippe Herbomel and co-workers (Demy et al., 2020) now argue for a function for Slc7a7 later in development. They show that macrophages lacking Slc7a7 are initially able to colonise the optic tectum and retina, the two sites with the most dense population of microglia in the larval zebrafish CNS, but died rapidly afterwards. Interestingly, microglial death coincides with a wave of neuronal cell death in the zebrafish CNS. The authors show that microglia and other tissue-resident macrophages die following sustained efferocytosis of dead cells, suggesting that Slc7a7 is required for macrophage survival in situations of increased efferocytic workload. Accordingly slc7a7 expression is induced in tissue-resident macrophages with sustained efferocytic activity. Collectively, these results identify a novel function for Slc7a7 in tissue-resident macrophage maintenance, which might be relevant to a human disease called lysinuric protein intolerance, which is caused by SLC7A7 deficiency, but whose etiology is not well understood.