If you are coming from the north on Highway 75, take the 275 exit toward St Petersburg (Exit 228) , but be careful to get off on the first exit, hwy 41. Follow hwy 41 all the way through Palmetto, across the Manatee river.  a couple of blocks after the river, you will see signs to the beaches.  that will be Manatee Ave.  Turn right onto Manatee and follow it all the way out to the island.
 

If you are coming from the south on Highway 75, Exit on Hwy 64 (exit 220B) and follow it all the way to the island.