The storm battered Haiti and the Dominican Republic with 70-mile-per-hour winds and flooding rains that sent thousands scrambling to higher ground.
At least four deaths were reported in Haiti, and in Cuba the storm's surge was damaging coastal property and forcing people to move inland.
Next in Isaac's path is south Florida and the vulnerable Florida Keys.
Tourists have been told to get out of Key West where the airport is closed and Florida's governor has declared a state of emergency.
Once the storm moves into the open waters of the Gulf of Mexico, forecasters say it will likely intensify into a hurricane before coming ashore somewhere along the coast of the Florida panhandle.
Isaac is already having an effect on plans for the Republican National Convention.
It was announced on Saturday that the Republican National Convention is being shortened. All of the events that were scheduled on Monday are being canceled, and the convention is going to be three days now instead of four.
The Illinois delegation is staying in Clearwater, Florida, about an hour drive from downtown Tampa.
It's that distance and the location of this island hotel that creates the challenge in extreme weather.
Two long, causeway bridges are the only way on and off the island, where not only Illinois, but thousands of other delegates are staying.
Illinois conventioneers clearly understand what's at stake and agree with the decision by Republican officials to scrap the first day of their national convention, bowing to Isaac's threat.
"I don't want to be on a bus and find myself going off a bridge because somebody decided to keep things going and it seems to me they're doing a good job planning for everybody's safety," said Margie Milone, GOP delegate from Bourbonnais.
"The party and the party leadership has done a pretty good job in warning us and I'm pretty sure we'll have people there waiting for us to get us out of here if there's an emergency happening," said Steve Kim, GOP delegate from Northbook.
It is not clear exactly what the new schedule will look like. Nominating day was supposed to be on Monday. We now understand that will happen on Tuesday. The RNC says it expects to have a revised schedule out Monday morning.
In case you have forgotten, this is not the first time this has happened. Four years ago, the first day was canceled because of hurricane Gustav.