The cytoplasm in mammalian cells is a battlefield between the host and invading microbes. Both the living organisms have evolved unique strategies for their survival. The host utilizes a specialized autophagy system, xenophagy, for the clearance of invading pathogens, whereas bacteria secrete proteins to defend and escape from the host xenophagy. Several molecules have been identified and their structural investigation has enabled the comprehension of these mechanisms at the molecular level. In this review, we focus on one example of host autophagy and the other of bacterial defense: the autophagy receptor, NDP52, in conjunction with the sugar receptor, galectin-8, plays a critical role in targeting the autophagy machinery against Salmonella; and the cysteine protease, RavZ secreted by Legionella pneumophila cleaves the LC3-PE on the phagophore membrane. The structure-function relationships of these two examples and the directions of future research will be discussed.