Glen Self, 83, of Tollhouse left his home around 11 a.m. Wednesday to go grocery shopping in Prather, but never returned home.
He was last seen driving a 2005 gray Mercury Montego with Oklahoma license plate A-F-X-0-3-2.
Self is considered at-risk because he is diabetic and does not have his medication.
The Highway Patrol has issued a Silver Alert for Fresno, Madera, Tulare, and Kings counties.
Anyone with information on his whereabouts is asked to call the Fresno County Sheriff's Office.