The baby boom generation is approaching the age of greatest risk for cognitive impairment and dementia. There is growing interest in strategies to modify the environment in midlife to increase the probability of maintaining cognitive health in late life. Several potentially modifiable risk factors have been studied in relation to cognitive impairment and dementia in late life, but methodological limitations of observational research have resulted in some inconsistencies across studies. The most promising strategies are maintaining cardiovascular health, engagement in mental, physical, and social activities, using alcohol in moderation, abstaining from tobacco use, and following a heart-healthy diet. Other factors that may influence cognitive health are occupational attainment, depression, personality, exposure to general anesthesia, head injury, postmenopausal hormone therapy, non-steroidal anti-inflammatory medications, and nutritional supplements such as antioxidants. Some long-term observational studies initiated in midlife or earlier, and some randomized controlled trials, have examined the effects of specific cognitive health promotion behaviors in midlife on the risk of cognitive impairment in late life. Overall, these studies provide limited support for risk reduction at this time. Recommendations and challenges for developing effective strategies to reduce the burden of cognitive impairment and dementia in the future are discussed.