The most common way to come here is from Samarkand. It is only 60 km and there are buses to the border, as well as taxis. Neither of those actually crosses the border, so arrange to be dropped at the Jartepa border post and find onward transport on the Tajik side. This shouldn't cause too many problems, except maybe when you arrive at the end of the day — the border closes around 6 PM and shared taxis dry up shortly after.
From the east, shared taxis run from Dushanbe to Penjikent in about five hours over the Anzob Tunnel and the Shahristan Pass — a spectacular but slow trip. The fare is around 200-250 somoni. There is also a small airport at Penjikent with sporadic domestic flights to Dushanbe; check Tajik Air for current schedules.