The Yarra Valley is a one-hour drive from Melbourne. The most direct route is to follow the Eastern Freeway from Melbourne until it becomes the Maroondah Highway, which leads to Healesville. Most of wine country is bordered by the Warburton Highway and the Melba Highway. The Maroondah runs between these two highways.
Cars are easily rented from Hertz (hertz.com.au), Avis (avis.com.au), and Europcar (europcar.com.au) at the airport and in Melbourne. Most Yarra Valley hotels and B&Bs can also arrange car services to take you to and from the city.
The Yarra Valley Visitor Information Centre, located in the old Healesville courthouse (011-61/3-5962-2600, visityarravalley.com.au), can supply detailed maps. Locals tend to rely on the Melway road atlas (ausway.com.au), and they'll often give you directions using grid numbers from Melway maps.
A note about Yarra Valley hotel rates: Weekends (Friday and Saturday nights) can be significantly more expensive than weekdays (Sunday through Thursday), and they may require at least a two-night stay or a package deal that includes meals or activities.