Shortages increased by more than 200 percent between 2006 and 2010, the report said, with a record 196 shortages last year.
Even more are expected in 2011, the GAO said.
"These shortages often force Americans to go without treatment," Sen. Tom Harkin, chairman of the Senate Committee on Health, Education, Labor and Pensions, told CNN.
On average, most shortages last more than nine months, the GAO said, with anesthetics and cancer drugs most often in short supply.
Manufacturing issues and technical difficulties are some of the biggest reasons for the drug shortages, it said.
More than half of the drugs on the shortage list are considered critical, meaning there are no other alternatives for them, the GAO said.