Guinea-Bissau is not the easiest country to reach, but it is not as isolated as you might expect.
By air: Osvaldo Vieira International Airport in Bissau receives flights from Lisbon (TAP Air Portugal), Dakar, and a handful of other West African capitals. The Lisbon connection is the most reliable route from Europe. There are no direct flights from North America or Asia -- you will need to connect through Lisbon or Dakar.
Overland from Senegal: The main border crossing is at Sao Domingos in the north. Bush taxis run from Ziguinchor in the Casamance region of Senegal to Bissau, a journey of around four to five hours depending on the state of the road and the border. This is a well-traveled route and straightforward enough.
Overland from Guinea (Conakry): The eastern border crossing connects to Koundara in Guinea. The road from Bafata to the border is rough and slow, and the journey to Kankan or Conakry is long and tiring. Only attempt this if you are comfortable with West African overland travel.
By sea: There are no regular international ferry services, though occasionally boats run between Bissau and the Casamance.
Whichever way you arrive, expect bureaucracy at the border. Have your visa, yellow fever certificate, and patience ready.