By plane
To get to Puerto Maldonado, one usually must travel from Lima - Cusco first before reaching the Padre Aldamiz PEM airport in Puerto Maldonado. Since domestic flights in Peru change so much, it is difficult to recommend carriers - however the most reliable seem to be LanPeru and StarPeru. Commercial flights in and out of Puerto Maldonado are almost always in the morning or early afternoon. The phone number at the airport is +51 084-571531.
Make sure to have your Yellow Fever Vaccination Card on you; local officials often ask for it even though it may or may not be "officially" required.
By Water
You can reach Puerto Maldonado from either the Tambopata or Madre de Dios rivers, but this is not likely for tourists.
By road
The road to Puerto Maldonado from Cuzco is improving since it is part of the Interoceanic highway, but currently the bus trip still takes 12 hours, so most tourist opt for the quicker and more comfortable 30-minute flight. Some lodges, including Wasai, even offer mountain biking tours from Cusco to Puerto Maldonado. This trip, however, is not for the casual beginner; it's a serious trek for serious athletes.