From the Boston area:
There are two approaches:
Take Route 3 North to Nashua, NH Exit 7. Take Route 101A West and then Route 101 West into the Region. This will bring you in through Peterborough.
Or, take Route 2 West to Route 140 in Gardner, MA. Follow Route 140 to Route 12 North. This will bring you in through Jaffrey (take Route 202) or Keene (continue on Route 12).
Driving time from Boston is approximately two hours.

From the Connecticut/New York area:
Follow Route 91 North into Brattleboro, VT Exit 3. Take Route 101 East into Keene, NH.
Driving time from Hartford is approximately two hours.

From Central Massachusetts or Rhode Island:
Follow Route 290 to Route 190 in Worcester. Continue on Route 190 to Route 2 West. Follow To Gardner, then take Route 140 North. Follow Route 140 to route 12 North. This will bring you in through Jaffrey, NH (take Route 202) or Keene (continue on Route 12.
Driving time from Worcester is approximately 90 minutes.

From Upstate New York or Vermont:
From Albany, NY follow Route 7 East to Bennington, VT. Take Route 9 East into Brattleboro, VT then Route 91 North to Exit 3. Follow Route 101 East into Keene, NH.
Driving time from Albany NY is approximately 2 hours.