By ferry. The Ceiba ferry from the east coast of the main island runs to Isabel Segunda about half a dozen times a day; the crossing takes 30 to 45 minutes. Tickets are very cheap. Schedules and reliability have improved in recent years but cancellations still happen, particularly outside the high winter season — check the day before.
By air. Small turboprops fly to Vieques airport (VQS) from San Juan's Isla Grande and Ceiba airports, run by Air Sunshine, Vieques Air Link, and Cape Air. The flight from San Juan is around 30 minutes and worth the price for the views over the east coast and Culebra.
By car. You cannot take a rental car from the main island; rentals on Vieques are arranged on arrival. A jeep is a sensible choice if you intend to drive to the more remote refuge beaches.