By Car -- To reach Esquipulas by car, take the Carretera al Atlántico (CA-9) out of Guatemala City to the crossroads at Río Hondo. Turn south here onto CA-10. The exit will be marked for Zacapa, Chiquimula, and Esquipulas. The trip should take 3 to 3 1/2 hours. There's a wonderful lookout located on the road into Esquipulas, about a mile before you hit the center of town. It will be on your left as you arrive, and it's worth a stop for the panoramic view of the city below.
By Bus -- Rutas Orientales, 19a Calle 8-18, Zona 1 (tel. 502/2220-9188 or 2251-2160), buses depart from Guatemala City's Zona 1 terminal every half-hour between 4:30am and 6pm. The fare is Q40 ($5.35/£2.65). Return buses leave Esquipulas from 11a Calle, just south of the Basílica, every half-hour between 2:30am and 5pm. The bus ride takes roughly 4 hours.
There are scores of taxis, motor taxis, and tuk tuks in Esquipulas. Most rides around town cost Q5 to Q15 (65¢-$2/35p-£1).
The city, and nearly all activity in it, is centered around the Basílica. The church, fronted by a park that's nearly 2 square blocks in size, sits on 11a Calle, the main road into and out of Esquipulas. All of the hotels and restaurants of interest to tourists are located within a 4-block radius of the Basílica. The north and south sides of the Basílica are packed with souvenir stands selling religious memorabilia, votive candles, and creative kitsch. There are several banks within a block or two of the Basílica, and the police station, post office, and town hall are located at the western end of 6a Avenida.