Ferries run several times a day to and from the mainland city of Puerto La Cruz and Margarita Island. During certain major holidays a ferry also runs back and forth from Caracas, the capital city of Venezuela. Limited routes stopping at Coche Island and Cumana are offered as well. It is recommended to try and take express ferries whenever possible for faster service. The first link below has a detailed route schedule.
Flights to the airport in the island's largest city, Porlamar, come mainly from Caracas, although other cities do connect to it, but less often. Miami is the only U.S. city that currently offers nonstop flights to Caracas. Follow the second link below for a basic flight chart for Del Caribe General Santiago Marino Airport in Porlamar.
Margarita is oftentimes a stop for cruise ships touring through the southern Caribbean. Seeing the island this way allows less time and flexibility, but it may be a preferred travel method for those who want to see more ports in the area. The third website listed below gives a sampling of possible cruise options that go to Margarita Island and one example of an itinerary that starts there.