Agios Nikolaos has no airport. The nearest is Heraklion Nikos Kazantzakis Airport, about 65 km to the west, which has extensive summer charter connections from across Europe and year-round scheduled flights from Athens. From the airport, KTEL buses run to Agios Nikolaos (1.5 hours, several daily); taxis take about an hour but are considerably more expensive.
By bus, KTEL runs regular services between Heraklion and Agios Nikolaos throughout the day. Buses also connect to Sitia to the east and Ierapetra to the south.
By car, the E75 highway from Heraklion takes about an hour in good conditions. In summer, traffic can extend this considerably. Having a car gives access to the Lassithi plateau, the far east of Crete, and the more remote beaches.