You can see a map of Napa Valley here. It shows the highways mentioned below.
Driving from San Francisco to Napa ValleyNapa Valley is more or less due north of San Francisco, but you have to get around the north end of the San Francisco Bay to get there. Either of the routes below takes slightly over an hour to drive from downtown San Francisco to the town of Napa, which is at the south end of the Napa Valley.
West Side of the Bay: Go over the Golden Gate Bridge north on US Hwy 101 to CA Hwy 37, then connection to CA Hwy 121 and CA Hwy 29. This route takes you through the southern end of Sonoma County and through the lush, rolling hills of the Carneros wine region. However, it also passes the the Raceway at Sears Point and on race days, the crowds can cause slow going through the Hwy 37/121 intersection.
East Side of the Bay: Take the Bay Bridge to I-80 north, exiting at American Canyon Rd. west, which connects to CA Hwy 29 north. Along this route, you'll get a chance to see the "ghost fleet" of mothballed US Navy ships languishing at the mouth of the Sacramento River.
San Francisco to Napa Valley by Public TransitThe easiest way to get from San Francisco to Napa using public transportation is to take the Vallejo Baylink Ferry from the San Francisco Ferry Building or Fisherman's Wharf Pier 41, then connect to the Napa Valley VINE bus system route 10, which can take you all the way to Calistoga. If you want to visit some wineries along the way, stick to the ones along CA Hwy 29 and contact the winery directly to ask where the nearest bus stop is. These services are mostly used by workday commuters and the number of trips they make per day is fewer on weekends - especially on Sundays.
San Francisco to Napa Valley on a Private TourA few San Francisco tour companies offer a personalized way to get to Napa Valley from San Francisco, taking small groups on adventures planned just for them. The two best are A Friend in Town and Blue Heron Tours. Both companies are locally owned by conscientious folks who do their best to make their customers happy and I occasionally do research trips with them.
All that personal attention means you might pay more than you would for a big-group bus tour, but if you're traveling with several other people, the price difference grows smaller. In any case, if your trip to Napa is a once-in-a-lifetime experience, why not get the most out of it?