This chapter examines the impacts of consuming a Western-style diet (WS-diet), rich in saturated fat, sugar and salt. Animal and human data convincingly show that a WS-diet causes hippocampal and prefrontal cortical impairment. Determining which component of a WS-diet is responsible is not currently clear. Several mechanisms may underpin these adverse effects on the brain: (1) reductions in neurotrophic factors; (2) neuroinflammation; (3) oxidative stress; (4) increased stress responsivity; (5) selective vulnerabilities in the hippocampal blood-brain barrier; and (6) changes to gut microbiota. The last one is intriguing as gut microbiota changes may impair the gut endothelial barrier allowing gut material to leak into the bloodstream, subsequently affecting the brain. Eating a WS-diet has also been linked to poorer mental health (anxiety/depression), it may exacerbate multiple sclerosis, and increased risk for Alzheimer’s and Parkinson’s disease. Finally, obesity may be a consequence of these adverse neural changes, leading to appetitive dysregulation and overeating.