This chapter highlights differences that exist between first language (L1) and second language (L2) reading contexts and readers. It explores how those differences might influence classroom instruction. Three major types of differences are linguistic and processing differences, individual and experiential differences, and socio-cultural and institutional differences. The chapter discusses the L1–L2 reading similarities. It outlines 15 ways L2 reading comprehension processes and instruction may differ from L1 contexts. The chapter presents six major differences between L1 and L2 readers involving vocabulary, grammar, discourse, orthography, and metalinguistic and metacognitive issues. At times L1 and L2 reading skills correlate not because of transfer of skills but because these reading skills rely on cognitive processing resources that are activated automatically whether one reads in the L1 or L2.