From the FDR Drive

Take the FDR to Houston Street exit, go west on Houston (it's only direction you can go)
After passing the Bowery, the next "major" street is Lafayette
Turn right (north) onto Lafayette and go one short block to Bleecker
Turn right onto Bleecker, and a few short blocks later make a right onto the Bowery
The club is a few doors down on the right side of Bowery

From Broadway/7th Avenue

Go south until you hit Bleecker Street (start watching for it after 14th Street)
Turn east onto Bleecker Street. Bleecker dead-ends on the Bowery &
The club is a few doors down.

From Canal Street

Take Canal to Lafayette and turn north:
(that will be a left if you're coming from the west side, a right if you're coming from the east side)
J ust past Houston Street, turn right onto Bleecker
A few short blocks later make a right onto the Bowery
The club is a few doors down Bowery

From the Williamsburg Bridge/Delancey Street

Continue West on Delancey St. until you hit the Bowery
Turn right (north) on Bowery
You'll see the club on your left shortly after crossing Houston Street
 

Since the surrounding blocks are quite short, you might want to start looking for parking before you actually get to the club. The area is pretty safe for parking on the street. If you can find a space, that is.

Sandwiches, soup, salads -- fresh, homemade. Delicious pastries and desserts. Truly excellent coffee! Unusual soft drinks. Juice, beer, wine, booze  at the bar. Plenty of upscale restaurants nearby, if your heart desires more.