There is a new long-distance bus terminal, the Terminal Terrestre, on the way to the airport (Via de Evitamiento 429, tel. 084/22-4471). This huge building is busy, safe, and crammed with all of the long-distance bus companies, bathrooms, and a few stores selling snacks. Companies generally open 6 a.m.–9 p.m. and accept reservations over the phone, with payment on the day of departure (you have to speak Spanish, though).
A recommended way to get to Puno  is with one of the tourist buses that visit the ruins on the way. These buses include a huge buffet lunch, English-speaking guide, and stops at most of the major ruins on the way. Inka Express (Plateros 320, tel. 084/24-7887, www.inkaexpress.com , US$50) makes stops in the exquisite colonial church of Andahuaylillas , the Inca ruins of Raqchi , and a buffet lunch stop in Sicuani . In the afternoon the bus stops at La Raya pass and the ruins of Pukará before arriving in Puno. The buses generally leave Cusco at 8 a.m. and arrive at 5 p.m. in Puno, include hotel pickup and drop-off, and even have oxygen tanks on board for altitude problems. There is a 10 percent discount for groups of more than four people.
For direct service to Puno, Ormeño (tel. 084/22-7501, www.grupo-ormeno.com ) has a daily bus leaving at 9 a.m., which arrives in Juliaca at 1:30 p.m. and Puno at 2 p.m. (US$14 for Royal Class, which has onboard food service and plusher seats than even the Imperial buses). Imexso (tel. 084/22-9126, imexso [at] terra [dot] com [dot] pe), for the most part, has good service and new buses, with English-language videos. Copacabana has a bus service leaving at 8 a.m. for US$5.
Many of the above companies offer transfer buses leaving for Bolivia, though some go through Desaguadero and others through Copacabana (launching point for Isla del Sol). Ormeño (tel. 084/22-7501) has a direct business-class bus (no meals) through Desaguadero to La Paz, leaving daily at 9 p.m. To head through Copacabana, try Tour Peru, which leaves 10 p.m. daily (US$28). Another recommended company for getting to Bolivia is Litoral, though there are many more options in Puno’s excellent Terminal Terrestre. The border crossing, which is open between 8 a.m. and 3 p.m., is quick and easy: Passengers need only get off the bus for a few minutes on each side of the border to have their passports stamped—remember to ask for the maximum number of days (usually 90).
Buses for the 20-hour haul to Lima  now head to Abancay  before crossing the mountains to the coast at Nazca and then heading north for Lima. Ormeño offers the extra-plush Royal Class service, which leaves at 10 a.m. and arrives in Lima the following day at 6 a.m. for US$50. There are also plain, one-story buses with a stop in Abancay. Another recommended company is Expreso Wari (tel. 084/24-7217, www.expresowari.com.pe ), which has buses with seats that recline into beds. Trips including meals leave at 12:30 p.m. and 8 p.m. for US$52. They also have a less luxurious service leaving at 2 p.m. and 4 p.m. for US$28. Cruz del Sur (tel. 084/24-8255) has a good Imperial service leaving at 3:30 p.m. and 6:30 p.m. Tepsa (tel. 084/22-4534, www.tepsa.com.pe ) is also a reliable option for Lima. The only company with transfer service through Abancay on to Ayacucho  is Expreso Los Chankas (tel. 084/24-2249).
The journey to Arequipa  via Juliaca  takes 8.5 hours. Cruz del Sur (tel. 084/24-8255) has Imperial buses that include dinner and bingo leaving at 2 p.m. for US$34, and Ormeño offers a similar-quality service. Enlaces (tel. 084/25-5333) and Cial (tel. 804/22-1201) also have Imperial buses leaving daily.
Most people who visit Colca  head to Arequipa first and then take the three-hour drive to Chivay , the Colca gateway, from there. There is an alternative, spectacular route on rocky roads that branches off from Sicuani and heads past Laguna Languilayo, the Tintaya copper and gold mine, and Condorama Dam on the Río Colca. This Cusco–Chivay route takes at least 11 hours, though more in rainy season, and it is best to do it on Saturday when buses are frequent. First head to Sicuani and scout for a Chivay direct bus or truck. If none is available, take local buses to El Descanso, Yauri, Chichas, and on to Chivay. (This 250-kilometer route between Sicuani and Chivay would also make an excellent mountain-bike journey.)
Another option from Colca is provided by the company Colca (tel. 084/26-3254), which has daily buses to Arequipa. This bus takes the traditional route through Juliaca and then stops at Pampa Cañaguas en route to Arequipa. The only direct option for Tacna, the border town for Chile, is Cruz del Sur (tel. 084/24-8255), which leaves at 4:30 p.m. and arrives at 8:30 a.m. the following day.
If you are a glutton for punishment you might want to consider the two-day bumpy but spectacular bus journey through Ocongate to Puerto Maldonado , the hardest of Cusco’s three jungle destinations. The best way to do this is to head to Urcos  and take a bus or truck onward from there. Atalaya, the gateway to the Parque Nacional Manu , is similarly hard to reach, but the journey can generally be made in a long day. Travelers must first head to Paucartambo. For Quillabamba, Ampay (tel. 084/24-9977) has buses leaving for the 8.5-hour journey for US$7 from the Terminal Terrestre.
Other options for Quillabamba and all other destinations in the Cusco region are the informal terminales where buses, combis, and colectivos leave when full. These are often located in places that are unsafe at night or early in the morning. They generally operate from 5 a.m. until as late as 7 p.m. Here is a list of terminales for destinations around Cusco . Most taxi drivers know where they are.
For Quillabamba, there is a roadside pickup spot, called a terminal de paso, at the last block of Avenida Antoñia Lorena, the principal exit road for the route that goes through the Sacred Valley  before heading over Abra Málaga into the jungle (7 hours, US$6).
For Urubamba , there are two options. Buses for the shorter, 1.5-hour route, through Chinchero , leave from the first block of Grau near the bridge (45 minutes, US$0.75 for Chinchero; 1.25 hours, US$1.50 for Urubamba). Collective taxis at Pavitos do the same route but go all the way to Ollantaytambo  (1.5 hours, US$3.50 pp).
Collective taxis and buses for Pisac  and Calca via Urubamba leave from Puputi and the last block of Tullumayo (one hour, US$1.5 for Pisac; 1.5 hours, US$1.50 for Urubamba).
For Sicuani , farther along this same route, buses also leave from Cultura but near Manuel Prado (3 hours, US$3.50).
For Paucartambo and the Manu jungle , buses leave from Cultura and Diagonal Angamos (3 hours, US$3).
Buses for Paruro leave from Belen and Grau (3 hours, US$3).