Many pathogenic bacteria can invade phagocytic and non-phagocytic cells and colonize them intracellularly, then become disseminated to other cells. The endocytic degradation pathway is thought to be the only prevention against such intracellular pathogens. Autophagy, a fundamental cellular homeostasis pathway that operates with the intracellular degradation/recycling system, causes the turnover of cellular components by delivering portions of the cytoplasm and organelles to lysosomes. Recently, we reported that autophagic degradation is a previously unrecognized effector of host innate immunity. Streptococcus pyogenes (Group A Streptococcus; GAS) successfully enters human epithelial cells via endocytosis. GAS immediately escapes from the endosomes to the cytoplasm and gains a replicative niche, after which GAS in the cytoplasm is trapped in autophagosome-like compartments and degraded upon fusion with lysosomes. This process indicates that autophagy plays a protective role in infectious diseases. We also found that autophagic degradation was induced against Staphylococcus aureus, while methicillin-resistant S. aureus were resistant to autophagic degradation. The present review focuses on the protective function of autophagy against bacterial invasion of cells.