Porto Velho airport is 7km north of town. There are daily direct flights to and from Rio Branco, Manaus, Cuiabá, Brasília and São Paulo with onward connections from there.
Slow boats down the Rio Madeira to Manaus (R$250 hammock, double cabin with fan/air-con R$700/900, 2½ days) leave Tuesdays, Wednesdays and Saturdays at 2pm from Porto Cai n’Água at the end of Rua 13 de Maio. You'll need your own hammock, and meals are available for purchase. Buy tickets from one of the four authorized brokers at the port, including Agência Monte Sinai. You can claim a spot and sleep on board two to three days before departure.
The bus station is 2km east of the center.
Eucatur runs daily buses to Rio Branco (R$75, eight to nine hours; 11am, 10pm, 10:05pm and midnight) and Cuiabá (R$170 to R$270; 25 hours; 2:30am, 5am, 6am, 9am, noon, 1:30pm and 8pm), with connection to Brasilia and beyond.
Real Norte serves Rio Branco (R$75; nine to ten hours) as well, with departures at 7am, noon, 9pm, 11pm and 11:55pm; service tends to be slower and the buses are older than Eucatur's. Real Norte also has services to Guajará-Mirim (R$63, six hours) at 6:30am, 10am, 2pm, 3pm, 6pm, 11:30pm and 1am.
Collective taxis serve Guajará-Mirim (per person R$100) and are much faster, usually around four hours. The price is based on a minimum of four passengers, so you may have to wait for the car to fill up.