From Melbourne Tullamarine airport take the Skybus Super Shuttle to Spencer Street for $16, and then transfer to the SkyBus Hotel Connection Service which will take you on to the Little Collins Hotel at no extra charge.
By car from Melbourne Airport, follow the Tullamarine Freeway and CityLink (toll road) to the Flemington Rd exit (before tolls start). Travel along Flemington Rd and turn right onto Elizabeth St and follow and turn left onto Collins St. Follow Collins St from the city for approximately 1km, and turn left into Spring St. Turn left into Little Collins St and Little Collins Hotel is on the left (#27).