Increased cytoplasmic lipid droplets (also known as lipid bodies or adiposomes) in nonadipocytic cells are commonly observed pathological features of a number of infectious diseases. Although the understanding of the functional significance of lipid droplets to host–pathogen interactions and microbial pathogenesis is still very limited, great advances in this growing field have been made in the past few years. Here, we review the recent findings that are starting to uncover the molecular mechanisms that regulate lipid accumulation into lipid droplets and the functions that this organelle may play during infection, with an emphasis on the potential implications of lipid droplets on human infectious diseases.