As major eukaryotic lipid storage organelles, lipid droplets (LDs) are metabolic hubs coordinating energy flux and building block distribution. Infectious patho-gens often promote accumulation and physically interact with LDs. The most accepted view is that host LDs are hijacked by invaders to draw on nutrients for host colonisation. However, unique traits such as biogenesis plasticity, dynamic proteome, signalling capacity, and ability to interact with other organelles endow LDs with competencies to face complex biological challenges. Here, we focus on published data suggesting that LDs are not usurped organelles but innate immu-nity first responders. By comparison with analogous mechanisms activated on LDs in nutrient-poor environments, our review supports the hypothesis that host LDs actively participate in immunometabolism, immune signalling, and microbial killing.