Brain imaging studies have identified a left-lateralized network of regions that are engaged when monolinguals read. However, for individuals who are native speakers of two languages, it is unclear whether this pattern of activity is maintained across both languages or if it deviates according to language-specific properties. We used functional magnetic resonance imaging to investigate single-word processing in Spanish and in English in 12 proficient early Spanish-English bilinguals matched in skill level in both languages. Word processing in Spanish engaged the left inferior frontal and left middle temporal gyri. Word processing in English activated the left inferior frontal, middle frontal, and fusiform gyri extending to inferior temporal gyrus and the right middle temporal gyrus extending into superior temporal sulcus. The comparison of reading in Spanish greater than reading in English revealed involvement of the left middle temporal gyrus extending into the superior temporal sulcus. English greater than Spanish, however, demonstrated greater engagement of the left middle frontal gyrus extending into the superior frontal gyrus. We conclude that although word processing in either language activates classical areas associated with reading, there are language-specific differences, which can be attributed to the disparity in orthographic transparency. English, an orthographically deep language, may require greater engagement of the frontal regions for phonological coding, whereas Spanish allows increased access to semantic processing via the left middle temporal areas. Together, these results suggest that bilinguals will show adjustments to the typical neural representation of reading as necessitated by the demands of the orthography.