Due to demographic changes, the number of older drivers is steadily increasing. Mobility is highly relevant for leading an independent life in the elderly. It largely depends on car driving, which is a complex task requiring a multitude of cognitive and motor skills vulnerable to age- related functional deterioration. The almost inevitable effects of senescence may be potentiated by age-related diseases, such as stroke or diabetes mellitus. Respective pharmacological treatment may cause side effects, additionally affecting driving safety. The present article reviews the impact of age-related diseases and drug treatment of these conditions on driving fitness in elderly drivers. In essence, we focus on diseases of the visual and auditory systems, diseases of the central nervous system (i.e., stroke, depression, dementia and mild cognitive disorder, and Parkinson’s disease), sleep disorders, as well as cardiovascular diseases, diabetes mellitus, musculoskeletal disorders, and frailty. We will outline the role of functional tests and the assessment of driving behavior (by a driving simulator or in real traffic), as well as the clinical interview including questions about frequency of (near) accidents, etc. in the evaluation of driving fitness of the elderly. We also address the impact of polypharmacy on driving fitness and end up with recommendations for physicians caring for older patients.