Nutritional deficiencies are a leading cause of human susceptibility to infectious diseases and antibiotic treatment failure. Specifically, intake of dietary lipids has changed dramatically over the last decades, yet our understanding of microbe-lipid interactions during infection is limited. Here, we study the balance between the making and taking of distinct fatty acids by bacterial pathogens and explore avenues to change the host fatty acid composition to promote bacterial clearance and enhance treatment efficacy. We have shown that bacterial pathogens have evolved efficient means to acquire host fatty acids, but that this is niche specific. Further, the ability of the human-adapted pathogen Streptococcus pneumoniae, to selectively acquire beneficial fatty acids, whilst concurrently preventing the uptake of poly-unsaturated fatty acids with antimicrobial activity, is not conserved across all bacterial pathogens. We have also interrogated the interaction of antimicrobial fatty acids found in fish oil and critical drug efflux systems in the microbial membrane, which was found to render the multidrug resistant pathogen Acinetobacter baumannii susceptible to various common antibiotics. Collectively, this work has revealed novel bacterial interactions with host fatty acids, thereby providing key insights into the suitability of bacterial fatty acid synthesis as a drug target. Further, the bacterial desire for fatty acids may present a possible weakness, as dietary lipid interventions could be used as strategy to prevent bacterial infections and optimise treatment efficacy.