Tajikistan is the least connected of all the Post-Soviet stans. It can be quite expensive to fly in, and it might make more sense for you to fly to Kashgar, Tashkent or Bishkek and make your way to Tajikistan overland.
Domestic flights go between Dushanbe and Khujand with Somon Air and Tajik Air. They both have online booking, but for regional flights these sites don’t seem to work. You will need to book through a travel agent.
The other domestic flight is the infamous Dushanbe – Khorog flight.
There are no other domestic flights.
Tashkent – Dushanbe flights
There has been flip-flopping on the issue of flights between the 2 capitals, but since April 11th, 2017, it seems like flights will be held regularly between the 2 capitals. There were no flights for more than 20 years due to mistrust between the 2 countries.
Expect confusion in the first few months.
We recommend having a look at the flight map of Dushanbe and Khujand airport. Almaty, Bishkek and Tashkent are the major airports of the region. If you are planning to make a tour of the region, it makes sense to fly to any of these and then make your way overland to Tajikistan.