Magnetic resonance (MRI) and positron emission tomography (PET) imaging have become vital tools in the preclinical and clinical armamentarium for identification, diagnosis, and assessment of Alzheimer’s disease (AD). The ε4 allele of the APOE gene is strongly linked to increased vulnerability to AD. MRI studies of APOEε4 carriers have increasingly demonstrated volumetric loss in brain regions known to be involved in AD progression. Advanced MRI techniques, such as diffusion MRI, further implicate microstructural abnormalities in gray and white matter regions in APOEε4 carriers even prior to the onset of cognitive disabilities. PET imaging of amyloid-β and tau have provided valuable insights into AD and how APOE genotypes modify disease progression, particularly prior to clinical symptomology. Existing and emerging new PET probes are discussed, including those related to neuroinflammation. Neuroinflammatory PET imaging reports in APOEε4 subjects found increased binding in brain regions known for increased levels of amyloid-β and tau. We also discuss the role of machine learning approaches that are being used to disentangle the role of APOEε4 and its contribution to AD progression in both MRI and PET neuroimaging. Neuroimaging will continue to play a significant role in the evaluation of AD patients and those at risk for AD that will undergo therapeutic interventions.