Alzheimer's disease (AD) is the leading cause of dementia in the United States and afflicts greater than 5.7 million Americans in 2018. Therapeutic options remain extremely limited to those that are symptom targeting, while no drugs have been approved for the modification or reversal of the disease itself. Risk factors for AD including aging, the female sex, as well as carrying an APOE4 genotype. These risk factors have been extensively examined in the literature, while less attention has been paid to modifiable risk factors, including lifestyle, and environmental risk factors such as exposures to air pollution and pesticides. This review highlights the most recent data on risk factors in AD and identifies gene by environment interactions that have been investigated. It also provides a suggested framework for a personalized therapeutic approach to AD, by combining genetic, environmental and lifestyle risk factors. Understanding modifiable risk factors and their interaction with non-modifiable factors (age, susceptibility alleles, and sex) is paramount for designing personalized therapeutic interventions.